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Published in: Tumor Biology 2/2014

01-02-2014 | Review

The function, mechanisms, and role of the genes PTEN and TP53 and the effects of asbestos in the development of malignant mesothelioma: a review focused on the genes' molecular mechanisms

Authors: Leonardo Vinícius Monteiro de Assis, Mauro César Isoldi

Published in: Tumor Biology | Issue 2/2014

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Abstract

The malignant mesothelioma is an aggressive form of cancer with a mean survival rate of less than a year. Moreover, environmental exposure to minerals is an important factor in the development of malignant mesothelioma (MM), especially the mineral asbestos, which has a well-documented role in MM, and more recently, the mineral erionite has been proven to be a strong carcinogenic inducer of MM. In addition, the virus simian virus 40 has been implicated as a co-carcinogenic player in MM. However, the molecular mechanisms involved in the pathogenesis of this cancer are still not fully understood. Indeed, it is known that several genes are altered or mutated in MM, among those are p16INK4A, p14ARF, and neurofibromatosis type II. Furthermore, TP53 has been reported to be mutated in the majority of the cancers; however, in MM, it is very uncommon mutations in this gene. Also, the PTEN gene has been shown to play an important role in endometrial cancer and glioblastoma, although the role of PTEN in MM has yet to be established. Taken altogether, this review focuses on the historical aspects, molecular mechanisms, interaction with other genes and proteins, and the role of these genes in MM. Lastly, this review questions the cancer theory of the two hits because the functions of both PTEN and TP53 are not fully explained by this theory.
Literature
3.
go back to reference van Meerbeeck JP, Gaafar R, Manegold C, Van Klaveren RJ, Van Marck EA, Vincent M, et al. Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol. 2005;23(28):6881–9.PubMed van Meerbeeck JP, Gaafar R, Manegold C, Van Klaveren RJ, Van Marck EA, Vincent M, et al. Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol. 2005;23(28):6881–9.PubMed
5.
go back to reference ATSDR. Public health statement—asbestos. Atlanta: Agency for Toxic and Disease Registry; 2001. ATSDR. Public health statement—asbestos. Atlanta: Agency for Toxic and Disease Registry; 2001.
6.
7.
go back to reference Eom M, Abdul-Ghafar J, Park SMHJ, Hong SW, Kwon KY, Ko ES, et al. No detection of simian virus 40 in malignant mesothelioma in Korea. Korean J Pathol. 2013;47(2):124–9.PubMedCentralPubMed Eom M, Abdul-Ghafar J, Park SMHJ, Hong SW, Kwon KY, Ko ES, et al. No detection of simian virus 40 in malignant mesothelioma in Korea. Korean J Pathol. 2013;47(2):124–9.PubMedCentralPubMed
8.
go back to reference Qi F, Carbone M, Yang H, Gaudino G. Simian virus 40 transformation, malignant mesothelioma and brain tumors. Expert Rev Respir Med. 2013;5(5):683–97. doi:10.1586/ers.11.51. Qi F, Carbone M, Yang H, Gaudino G. Simian virus 40 transformation, malignant mesothelioma and brain tumors. Expert Rev Respir Med. 2013;5(5):683–97. doi:10.​1586/​ers.​11.​51.
10.
go back to reference Kroczynska B, Cutrone R, Bocchetta M, Yang H, Elmishad AG, Vacek P, et al. Crocidolite asbestos and SV40 are cocarcinogens in human mesothelial cells and in causing mesothelioma in hamsters. Proc Natl Acad Sci. 2006;103(38):14128–33. doi:10.1073/pnas.0604544103.PubMed Kroczynska B, Cutrone R, Bocchetta M, Yang H, Elmishad AG, Vacek P, et al. Crocidolite asbestos and SV40 are cocarcinogens in human mesothelial cells and in causing mesothelioma in hamsters. Proc Natl Acad Sci. 2006;103(38):14128–33. doi:10.​1073/​pnas.​0604544103.PubMed
11.
go back to reference Manfredi JJ, Dong J, Liu W-J, Resnick-Silverman L, Qiao R, Chahinian P, et al. Evidence against a role for SV40 in human mesothelioma. Cancer Res. 2005;65(7):2602–9.PubMed Manfredi JJ, Dong J, Liu W-J, Resnick-Silverman L, Qiao R, Chahinian P, et al. Evidence against a role for SV40 in human mesothelioma. Cancer Res. 2005;65(7):2602–9.PubMed
13.
go back to reference Jean D, Daubriac J, Le Pimpec-Barthes F, Galateau-Salle F, Jaurand M-C. Molecular changes in mesothelioma with an impact on prognosis and treatment. Arch Pathol Lab Med. 2012;136(3):277–93. doi:10.5858/arpa.2011-0215-RA.PubMed Jean D, Daubriac J, Le Pimpec-Barthes F, Galateau-Salle F, Jaurand M-C. Molecular changes in mesothelioma with an impact on prognosis and treatment. Arch Pathol Lab Med. 2012;136(3):277–93. doi:10.​5858/​arpa.​2011-0215-RA.PubMed
14.
go back to reference Hu Q, Akatsuka S, Yamashita Y, Ohara H, Nagai H, Okazaki Y, et al. Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma. Lab Investig. 2010;90(3):360–73.PubMed Hu Q, Akatsuka S, Yamashita Y, Ohara H, Nagai H, Okazaki Y, et al. Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma. Lab Investig. 2010;90(3):360–73.PubMed
16.
go back to reference Sekido Y, Pass HI, Bader S, Mew DJY, Christman MF, Gazdar AF, et al. Neurofibromatosis Type 2 (NF2) gene is somatically mutated in mesothelioma but not in lung cancer. Cancer Res. 1995;55(6):1227–31.PubMed Sekido Y, Pass HI, Bader S, Mew DJY, Christman MF, Gazdar AF, et al. Neurofibromatosis Type 2 (NF2) gene is somatically mutated in mesothelioma but not in lung cancer. Cancer Res. 1995;55(6):1227–31.PubMed
18.
go back to reference Suzuki Y, Murakami H, Kawaguchi K, Tanigushi T, Fujii M, Shinjo K, et al. Activation of the PI3K-AKT pathway in human malignant mesothelioma cells. Mol Med Rep. 2009;2(2):181–8.PubMed Suzuki Y, Murakami H, Kawaguchi K, Tanigushi T, Fujii M, Shinjo K, et al. Activation of the PI3K-AKT pathway in human malignant mesothelioma cells. Mol Med Rep. 2009;2(2):181–8.PubMed
19.
go back to reference Altomare DA, You H, Xiao GH, Ramos-Nino ME, Skele KL, De Rienzo A, et al. Human and mouse mesotheliomas exhibit elevated AKT/PKB activity, which can be targeted pharmacologically to inhibit tumor cell growth. Oncogene. 2005;24(40):6080–9. doi:10.1038/sj.onc.1208744.PubMed Altomare DA, You H, Xiao GH, Ramos-Nino ME, Skele KL, De Rienzo A, et al. Human and mouse mesotheliomas exhibit elevated AKT/PKB activity, which can be targeted pharmacologically to inhibit tumor cell growth. Oncogene. 2005;24(40):6080–9. doi:10.​1038/​sj.​onc.​1208744.PubMed
20.
21.
go back to reference Wilson SM, Barbone D, Yang T-M, Jablons DM, Bueno R, Sugarbaker DJ, et al. mTOR mediates survival signals in malignant mesothelioma grown as tumor fragment spheroids. Am J Respir Cell Mol Biol. 2008;39(5):576–83. doi:10.1165/rcmb.2007-0460OC.PubMed Wilson SM, Barbone D, Yang T-M, Jablons DM, Bueno R, Sugarbaker DJ, et al. mTOR mediates survival signals in malignant mesothelioma grown as tumor fragment spheroids. Am J Respir Cell Mol Biol. 2008;39(5):576–83. doi:10.​1165/​rcmb.​2007-0460OC.PubMed
22.
23.
go back to reference Opitz I, Soltermann A, Abaecherli M, Hinterberger M, Probst-Hensch N, Stahel R, et al. PTEN expression is a strong predictor of survival in mesothelioma patients. Eur J Cardiothorac Surg. 2008;33(3):501–5. doi:10.1016/j.ejcts.2007.09.045. Opitz I, Soltermann A, Abaecherli M, Hinterberger M, Probst-Hensch N, Stahel R, et al. PTEN expression is a strong predictor of survival in mesothelioma patients. Eur J Cardiothorac Surg. 2008;33(3):501–5. doi:10.​1016/​j.​ejcts.​2007.​09.​045.
24.
go back to reference Frezza C, Martins CP. From tumor prevention to therapy: empowering p53 to fight back. Drug Resist Updat. 2012;15(5):258–67. Reviews and commentaries in antimicrobial and anticancer chemotherapy.PubMed Frezza C, Martins CP. From tumor prevention to therapy: empowering p53 to fight back. Drug Resist Updat. 2012;15(5):258–67. Reviews and commentaries in antimicrobial and anticancer chemotherapy.PubMed
26.
go back to reference Freeman DJ, Li AG, Wei G, Li H-H, Kertesz N, Lesche R, et al. PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms. Cancer Cell. 2003;3(2):117–30. doi:10.1016/S1535-6108(03)00021-7.PubMed Freeman DJ, Li AG, Wei G, Li H-H, Kertesz N, Lesche R, et al. PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms. Cancer Cell. 2003;3(2):117–30. doi:10.​1016/​S1535-6108(03)00021-7.PubMed
27.
go back to reference Salmena L, Carracedo A, Pandolfi PP. Tenets of PTEN tumor suppression. Cell. 2008;133(3):403–14.PubMed Salmena L, Carracedo A, Pandolfi PP. Tenets of PTEN tumor suppression. Cell. 2008;133(3):403–14.PubMed
28.
go back to reference Heyn H, Carmona FJ, Gomez A, Ferreira HJ, Bell JT, Sayols S, et al. DNA methylation profiling in breast cancer discordant identical twins identifies DOK7 as novel epigenetic biomarker. Carcinogenesis. 2013;34(1):102–8. doi:10.1093/carcin/bgs321.PubMed Heyn H, Carmona FJ, Gomez A, Ferreira HJ, Bell JT, Sayols S, et al. DNA methylation profiling in breast cancer discordant identical twins identifies DOK7 as novel epigenetic biomarker. Carcinogenesis. 2013;34(1):102–8. doi:10.​1093/​carcin/​bgs321.PubMed
30.
go back to reference Esteller M, Corn PG, Baylin SB, Herman JG. A gene hypermethylation profile of human cancer. Cancer Res. 2001;61(8):3225–9.PubMed Esteller M, Corn PG, Baylin SB, Herman JG. A gene hypermethylation profile of human cancer. Cancer Res. 2001;61(8):3225–9.PubMed
31.
32.
go back to reference Hama R, Watanabe Y, Shinada K, Yamada Y, Ogata Y, Yoshida Y, et al. Characterization of DNA hypermethylation in two cases of peritoneal mesothelioma. Tumor Biol. 2012;33(6):2031–40. doi:10.1007/s13277-012-0462-8. Hama R, Watanabe Y, Shinada K, Yamada Y, Ogata Y, Yoshida Y, et al. Characterization of DNA hypermethylation in two cases of peritoneal mesothelioma. Tumor Biol. 2012;33(6):2031–40. doi:10.​1007/​s13277-012-0462-8.
35.
go back to reference Hansen J, de Klerk NH, Musk AW, Hobbs MS. Environmental exposure to crocidolite and mesothelioma: exposure-response relationships. Am J Respir Crit Care Med. 1998;157(1):69–75.PubMed Hansen J, de Klerk NH, Musk AW, Hobbs MS. Environmental exposure to crocidolite and mesothelioma: exposure-response relationships. Am J Respir Crit Care Med. 1998;157(1):69–75.PubMed
36.
go back to reference Luo S, Liu X, Mu S, Tsai SP, Wen CP. Asbestos related diseases from environmental exposure to crocidolite in Da-yao, China. I. Review of exposure and epidemiological data. Occup Environ Med. 2003;60(1):35–42. doi:10.1136/oem.60.1.35.PubMed Luo S, Liu X, Mu S, Tsai SP, Wen CP. Asbestos related diseases from environmental exposure to crocidolite in Da-yao, China. I. Review of exposure and epidemiological data. Occup Environ Med. 2003;60(1):35–42. doi:10.​1136/​oem.​60.​1.​35.PubMed
37.
go back to reference Powers A, Carbone M. The role of environmental carcinogens, viruses and genetic predisposition in the pathogenesis of mesothelioma. Cancer Biol Ther. 2002;1(4):348–53.PubMed Powers A, Carbone M. The role of environmental carcinogens, viruses and genetic predisposition in the pathogenesis of mesothelioma. Cancer Biol Ther. 2002;1(4):348–53.PubMed
39.
go back to reference Pedra F, Tambellini AT, Pereira BB, Carioca da Costa AC, Albuquerque de Castro H. Mesothelioma mortality in Brazil, 1980–2003. Int J Occup Environ Health. 2008;14(3):170–5.PubMed Pedra F, Tambellini AT, Pereira BB, Carioca da Costa AC, Albuquerque de Castro H. Mesothelioma mortality in Brazil, 1980–2003. Int J Occup Environ Health. 2008;14(3):170–5.PubMed
40.
go back to reference Roggli VL, Oury TD, Moffat EJ. Malignant mesothelioma in women. Anat Pathol. 1997;2:147–63.PubMed Roggli VL, Oury TD, Moffat EJ. Malignant mesothelioma in women. Anat Pathol. 1997;2:147–63.PubMed
41.
go back to reference Price B, Ware A. Mesothelioma trends in the United States: an update based on surveillance, epidemiology, and end results program data for 1973 through 2003. Am J Epidemiol. 2004;159(2):107–12. doi:10.1093/aje/kwh025.PubMed Price B, Ware A. Mesothelioma trends in the United States: an update based on surveillance, epidemiology, and end results program data for 1973 through 2003. Am J Epidemiol. 2004;159(2):107–12. doi:10.​1093/​aje/​kwh025.PubMed
43.
go back to reference Magnani C, Agudo A, Gonzalez CA, Andrion A, Calleja A, Chellini E, et al. Multicentric study on malignant pleural mesothelioma and non-occupational exposure to asbestos. Br J Cancer. 2000;83(1):104–11.PubMedCentralPubMed Magnani C, Agudo A, Gonzalez CA, Andrion A, Calleja A, Chellini E, et al. Multicentric study on malignant pleural mesothelioma and non-occupational exposure to asbestos. Br J Cancer. 2000;83(1):104–11.PubMedCentralPubMed
44.
go back to reference Yang H, Bocchetta M, Kroczynska B, Elmishad AG, Chen Y, Liu Z, et al. TNF-α inhibits asbestos-induced cytotoxicity via a NF-κB-dependent pathway, a possible mechanism for asbestos-induced oncogenesis. Proc Natl Acad Sci. 2006;103(27):10397–402. doi:10.1073/pnas.0604008103.PubMed Yang H, Bocchetta M, Kroczynska B, Elmishad AG, Chen Y, Liu Z, et al. TNF-α inhibits asbestos-induced cytotoxicity via a NF-κB-dependent pathway, a possible mechanism for asbestos-induced oncogenesis. Proc Natl Acad Sci. 2006;103(27):10397–402. doi:10.​1073/​pnas.​0604008103.PubMed
46.
47.
go back to reference Xu A, Zhou H, Yu DZ, Hei TK. Mechanisms of the genotoxicity of crocidolite asbestos in mammalian cells: implication from mutation patterns induced by reactive oxygen species. Environ Health Perspect. 2002;110(10):1003–8.PubMedCentralPubMed Xu A, Zhou H, Yu DZ, Hei TK. Mechanisms of the genotoxicity of crocidolite asbestos in mammalian cells: implication from mutation patterns induced by reactive oxygen species. Environ Health Perspect. 2002;110(10):1003–8.PubMedCentralPubMed
48.
go back to reference Weiner S, Neragi-Miandoab S. Pathogenesis of malignant pleural mesothelioma and the role of environmental and genetic factors. J Carcinog. 2008;7(1):3.PubMedCentralPubMed Weiner S, Neragi-Miandoab S. Pathogenesis of malignant pleural mesothelioma and the role of environmental and genetic factors. J Carcinog. 2008;7(1):3.PubMedCentralPubMed
50.
go back to reference Tweedale G. Asbestos and its lethal legacy. Nat Rev Cancer. 2002;2(4):311–4.PubMed Tweedale G. Asbestos and its lethal legacy. Nat Rev Cancer. 2002;2(4):311–4.PubMed
51.
53.
go back to reference Ben David Y, Prideaux VR, Chow V, Benchimol S, Berstein A. Inactivation of the p53 oncogene by internal deletion or retroviral integration in erythroleukemic cell lines induced by Friend leukemia virus. Oncogene. 1988;3(2):179–85.PubMed Ben David Y, Prideaux VR, Chow V, Benchimol S, Berstein A. Inactivation of the p53 oncogene by internal deletion or retroviral integration in erythroleukemic cell lines induced by Friend leukemia virus. Oncogene. 1988;3(2):179–85.PubMed
55.
go back to reference Mowat M, Cheng A, Kimura N, Bernstein A, Benchimol S. Rearrangements of the cellular p53 gene in erythroleukaemic cells transformed by Friend virus. Nature. 1985;314(6012):633–6.PubMed Mowat M, Cheng A, Kimura N, Bernstein A, Benchimol S. Rearrangements of the cellular p53 gene in erythroleukaemic cells transformed by Friend virus. Nature. 1985;314(6012):633–6.PubMed
56.
go back to reference Vogelstein B, Lane D. Surfing the p53 network. Nature. 2000;408(6810):307.PubMed Vogelstein B, Lane D. Surfing the p53 network. Nature. 2000;408(6810):307.PubMed
57.
go back to reference Srivastava S, Zou Z, Pirollo K, Blattner W, Chang EH. Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature. 1990;348(6303):747–9. doi:10.1038/348747a0.PubMed Srivastava S, Zou Z, Pirollo K, Blattner W, Chang EH. Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature. 1990;348(6303):747–9. doi:10.​1038/​348747a0.PubMed
58.
go back to reference Shaw P, Bovey R, Tardy S, Sahli R, Sordat B, Costa J. Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line. Proc Natl Acad Sci. 1992;89(10):4495–9.PubMed Shaw P, Bovey R, Tardy S, Sahli R, Sordat B, Costa J. Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line. Proc Natl Acad Sci. 1992;89(10):4495–9.PubMed
59.
go back to reference Yonish-Rouach E, Resnftzky D, Lotem J, Sachs L, Kimchi A, Oren M. Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature. 1991;352(6333):345.PubMed Yonish-Rouach E, Resnftzky D, Lotem J, Sachs L, Kimchi A, Oren M. Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature. 1991;352(6333):345.PubMed
60.
go back to reference Ventura A, Kirsch DG, McLaughlin ME, Tuveson DA, Grimm J, Lintault L, et al. Restoration of p53 function leads to tumour regression in vivo. Nature. 2007;445(7128):661.PubMed Ventura A, Kirsch DG, McLaughlin ME, Tuveson DA, Grimm J, Lintault L, et al. Restoration of p53 function leads to tumour regression in vivo. Nature. 2007;445(7128):661.PubMed
61.
go back to reference Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V, et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature. 2007;445(7128):656.PubMed Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V, et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature. 2007;445(7128):656.PubMed
62.
go back to reference Menendez D, Inga A, Resnick MA. The expanding universe of p53 targets. Nat Rev Cancer. 2009;9(10):724–37.PubMed Menendez D, Inga A, Resnick MA. The expanding universe of p53 targets. Nat Rev Cancer. 2009;9(10):724–37.PubMed
64.
go back to reference Oliner JD, Pietenpol JA, Thiagalingam S, Gyuris J, Kinzler KW, Vogelstein B. Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature. 1993;362(6423):857–60.PubMed Oliner JD, Pietenpol JA, Thiagalingam S, Gyuris J, Kinzler KW, Vogelstein B. Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature. 1993;362(6423):857–60.PubMed
65.
go back to reference Chène P. Inhibiting the p53–MDM2 interaction: an important target for cancer therapy. Nat Rev Cancer. 2003;3(2):102.PubMed Chène P. Inhibiting the p53–MDM2 interaction: an important target for cancer therapy. Nat Rev Cancer. 2003;3(2):102.PubMed
67.
go back to reference Peng Z. Current status of gendicine in China: recombinant human Ad-p53 agent for treatment of cancers. Hum Gene Ther. 2005;16(9):16–27. Peng Z. Current status of gendicine in China: recombinant human Ad-p53 agent for treatment of cancers. Hum Gene Ther. 2005;16(9):16–27.
68.
go back to reference Metcalf RA, Welsh JA, Bennett WP, Seddon MB, Lehman TA, Pelin K, et al. p53 and Kirsten-ras mutations in human mesothelioma cell lines. Cancer Res. 1992;52(9):2610–5.PubMed Metcalf RA, Welsh JA, Bennett WP, Seddon MB, Lehman TA, Pelin K, et al. p53 and Kirsten-ras mutations in human mesothelioma cell lines. Cancer Res. 1992;52(9):2610–5.PubMed
70.
go back to reference Vivo C, Lecomte C, Levy F, Leroy K, Kirova Y, Renier A, et al. Cell cycle checkpoint status in human malignant mesothelioma cell lines: response to gamma radiation. Br J Cancer. 2003;88(3):388–95.PubMedCentralPubMed Vivo C, Lecomte C, Levy F, Leroy K, Kirova Y, Renier A, et al. Cell cycle checkpoint status in human malignant mesothelioma cell lines: response to gamma radiation. Br J Cancer. 2003;88(3):388–95.PubMedCentralPubMed
72.
go back to reference Steck PA, Pershouse MA, Jasser SA, Yung WKA, Lin H, Ligon AH, et al. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet. 1997;15(4):356–62.PubMed Steck PA, Pershouse MA, Jasser SA, Yung WKA, Lin H, Ligon AH, et al. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet. 1997;15(4):356–62.PubMed
73.
go back to reference Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997;275(5308):1943–7.PubMed Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997;275(5308):1943–7.PubMed
74.
go back to reference Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 2012;13(5):283–96.PubMed Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 2012;13(5):283–96.PubMed
76.
go back to reference Cristofano AD, Pesce B, Cordon-Cardo C, Pandolfi PP. Pten is essential for embryonic development and tumour suppression. Nat Genet. 1998;19(4):348–55. doi:10.1038/1235.PubMed Cristofano AD, Pesce B, Cordon-Cardo C, Pandolfi PP. Pten is essential for embryonic development and tumour suppression. Nat Genet. 1998;19(4):348–55. doi:10.​1038/​1235.PubMed
77.
go back to reference Suzuki A, de la Pompa JL, Stambolic V, Elia AJ, Sasaki T, Barrantes IDB. High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol. 1998;8(21):1169–78.PubMed Suzuki A, de la Pompa JL, Stambolic V, Elia AJ, Sasaki T, Barrantes IDB. High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol. 1998;8(21):1169–78.PubMed
78.
go back to reference Whang YE, Wu X, Suzuki H, Reiter RE, Tran C, Robert L, et al. Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression. Proc Natl Acad Sci. 1998;95(9):5246–50.PubMed Whang YE, Wu X, Suzuki H, Reiter RE, Tran C, Robert L, et al. Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression. Proc Natl Acad Sci. 1998;95(9):5246–50.PubMed
79.
go back to reference Lachyankar MB, Sultana N, Schonhoff CM, Mitra P, Poluha W, Lambert S, et al. A role for nuclear PTEN in neuronal differentiation. J Neurosci. 2000;20(4):1404–13.PubMed Lachyankar MB, Sultana N, Schonhoff CM, Mitra P, Poluha W, Lambert S, et al. A role for nuclear PTEN in neuronal differentiation. J Neurosci. 2000;20(4):1404–13.PubMed
80.
go back to reference Ginn-Pease ME, Eng C. Increased nuclear phosphatase and tensin homologue deleted on chromosome 10 is associated with G0-G1 in MCF-7 Cells. Cancer Res. 2003;63(2):282–6.PubMed Ginn-Pease ME, Eng C. Increased nuclear phosphatase and tensin homologue deleted on chromosome 10 is associated with G0-G1 in MCF-7 Cells. Cancer Res. 2003;63(2):282–6.PubMed
81.
go back to reference Déléris P, Bacqueville D, Gayral SP, Carrez L, Salles J-P, Perret B, et al. SHIP-2 and PTEN are expressed and active in vascular smooth muscle cell nuclei, but only SHIP-2 is associated with nuclear speckles. J Biol Chem. 2003;278(40):38884–91.PubMed Déléris P, Bacqueville D, Gayral SP, Carrez L, Salles J-P, Perret B, et al. SHIP-2 and PTEN are expressed and active in vascular smooth muscle cell nuclei, but only SHIP-2 is associated with nuclear speckles. J Biol Chem. 2003;278(40):38884–91.PubMed
82.
go back to reference Trotman LC, Niki M, Dotan ZA, Koutcher JA, Di Cristofano A, Xiao A, et al. Pten dose dictates cancer progression in the prostate. PLoS Biol. 2003;1(3):e59.PubMedCentralPubMed Trotman LC, Niki M, Dotan ZA, Koutcher JA, Di Cristofano A, Xiao A, et al. Pten dose dictates cancer progression in the prostate. PLoS Biol. 2003;1(3):e59.PubMedCentralPubMed
83.
go back to reference Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133(2):647–58.PubMed Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133(2):647–58.PubMed
84.
go back to reference García JM, Silva J, Peña C, Garcia V, Rodríguez R, Cruz MA, et al. Promoter methylation of the PTEN gene is a common molecular change in breast cancer. Genes Chromosom Cancer. 2004;41(2):117–24. doi:10.1002/gcc.20062.PubMed García JM, Silva J, Peña C, Garcia V, Rodríguez R, Cruz MA, et al. Promoter methylation of the PTEN gene is a common molecular change in breast cancer. Genes Chromosom Cancer. 2004;41(2):117–24. doi:10.​1002/​gcc.​20062.PubMed
85.
go back to reference Torres J, Pulido R. The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus: implications for PTEN stability to proteasome-mediated degradation. J Biol Chem. 2001;276(2):993–8. doi:10.1074/jbc.M009134200.PubMed Torres J, Pulido R. The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus: implications for PTEN stability to proteasome-mediated degradation. J Biol Chem. 2001;276(2):993–8. doi:10.​1074/​jbc.​M009134200.PubMed
87.
go back to reference Leslie NR, Bennett D, Lindsay YE, Stewart H, Gray A, Downes CP. Redox regulation of PI 3-kinase signalling via inactivation of PTEN. EMBO J. 2003;22(20):5501–10.PubMed Leslie NR, Bennett D, Lindsay YE, Stewart H, Gray A, Downes CP. Redox regulation of PI 3-kinase signalling via inactivation of PTEN. EMBO J. 2003;22(20):5501–10.PubMed
88.
go back to reference Faivre S, Kroemer G, Raymond E. Current development of mTOR inhibitors as anticancer agents. Nat Rev Drug Discov. 2006;5(8):671–88.PubMed Faivre S, Kroemer G, Raymond E. Current development of mTOR inhibitors as anticancer agents. Nat Rev Drug Discov. 2006;5(8):671–88.PubMed
89.
go back to reference Borders EB, Bivona C, Medina PJ. Mammalian target of rapamycin: biological function and target for novel anticancer agents. Am J Health Syst Pharm. 2010;67(24):2095–106. doi:10.2146/ajhp100020.PubMed Borders EB, Bivona C, Medina PJ. Mammalian target of rapamycin: biological function and target for novel anticancer agents. Am J Health Syst Pharm. 2010;67(24):2095–106. doi:10.​2146/​ajhp100020.PubMed
90.
go back to reference Holmes D. PI3K pathway inhibitors approach junction. Nat Rev Drug Discov. 2011;10(8):563–4.PubMed Holmes D. PI3K pathway inhibitors approach junction. Nat Rev Drug Discov. 2011;10(8):563–4.PubMed
92.
go back to reference Shen WH, Balajee AS, Wang J, Wu H, Eng C, Pandolfi PP, et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell. 2007;128(1):157–70.PubMed Shen WH, Balajee AS, Wang J, Wu H, Eng C, Pandolfi PP, et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell. 2007;128(1):157–70.PubMed
93.
go back to reference Chung J-H, Ostrowski MC, Romigh T, Minaguchi T, Waite KA, Eng C. The ERK1/2 pathway modulates nuclear PTEN-mediated cell cycle arrest by cyclin D1 transcriptional regulation. Hum Mol Genet. 2006;15(17):2553–9. doi:10.1093/hmg/ddl177.PubMed Chung J-H, Ostrowski MC, Romigh T, Minaguchi T, Waite KA, Eng C. The ERK1/2 pathway modulates nuclear PTEN-mediated cell cycle arrest by cyclin D1 transcriptional regulation. Hum Mol Genet. 2006;15(17):2553–9. doi:10.​1093/​hmg/​ddl177.PubMed
94.
go back to reference Li AG, Piluso LG, Cai X, Wei G, Sellers WR, Liu X. Mechanistic insights into maintenance of high p53 acetylation by PTEN. Mol Cell. 2006;23(4):575–87.PubMed Li AG, Piluso LG, Cai X, Wei G, Sellers WR, Liu X. Mechanistic insights into maintenance of high p53 acetylation by PTEN. Mol Cell. 2006;23(4):575–87.PubMed
95.
96.
go back to reference Mayo LD, Donner DB. A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of MDM2 from the cytoplasm to the nucleus. Proc Natl Acad Sci. 2001;98(20):11598–603. doi:10.1073/pnas.181181198.PubMed Mayo LD, Donner DB. A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of MDM2 from the cytoplasm to the nucleus. Proc Natl Acad Sci. 2001;98(20):11598–603. doi:10.​1073/​pnas.​181181198.PubMed
97.
98.
go back to reference Alimonti A, Nardella C, Chen Z, Clohessy JG, Carracedo A, Trotman LC, et al. A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis. J Clin Invest. 2010;120(3):681–93. doi:10.1172/jci40535.PubMedCentralPubMed Alimonti A, Nardella C, Chen Z, Clohessy JG, Carracedo A, Trotman LC, et al. A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis. J Clin Invest. 2010;120(3):681–93. doi:10.​1172/​jci40535.PubMedCentralPubMed
99.
100.
go back to reference Tanaka M, Rosser CJ, Grossman HB. PTEN gene therapy induces growth inhibition and increases efficacy of chemotherapy in prostate cancer. Cancer Detect Prev. 2005;29(2):170–4.PubMed Tanaka M, Rosser CJ, Grossman HB. PTEN gene therapy induces growth inhibition and increases efficacy of chemotherapy in prostate cancer. Cancer Detect Prev. 2005;29(2):170–4.PubMed
101.
go back to reference Saito Y, Swanson X, Mhashilkar AM, Oida Y, Schrock R, Branch CD, et al. Adenovirus-mediated transfer of the PTEN gene inhibits human colorectal cancer growth in vitro and in vivo. Gene Ther. 2003;10(23):1961–9.PubMed Saito Y, Swanson X, Mhashilkar AM, Oida Y, Schrock R, Branch CD, et al. Adenovirus-mediated transfer of the PTEN gene inhibits human colorectal cancer growth in vitro and in vivo. Gene Ther. 2003;10(23):1961–9.PubMed
102.
go back to reference Garland LL, Rankin C, Gandara DR, Rivkin SE, Scott KM, Nagle RB, et al. Phase II study of erlotinib in patients with malignant pleural mesothelioma: a Southwest Oncology Group study. J Clin Oncol. 2007;25(17):2406–13. doi:10.1200/jco.2006.09.7634.PubMed Garland LL, Rankin C, Gandara DR, Rivkin SE, Scott KM, Nagle RB, et al. Phase II study of erlotinib in patients with malignant pleural mesothelioma: a Southwest Oncology Group study. J Clin Oncol. 2007;25(17):2406–13. doi:10.​1200/​jco.​2006.​09.​7634.PubMed
103.
go back to reference Knudson AJ. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci. 1971;68(4):820–3.PubMed Knudson AJ. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci. 1971;68(4):820–3.PubMed
104.
go back to reference Fung YK, Murphree AL, T'Ang A, Qian J, Hinrichs SH, Benedict WF. Structural evidence for the authenticity of the human retinoblastoma gene. Science. 1987;236(4809):1657–61.PubMed Fung YK, Murphree AL, T'Ang A, Qian J, Hinrichs SH, Benedict WF. Structural evidence for the authenticity of the human retinoblastoma gene. Science. 1987;236(4809):1657–61.PubMed
105.
go back to reference Venkatachalam S, Shi Y-P, Jones SN, Vogel H, Bradley A, Pinkel D, et al. Retention of wild-type p53 in tumors from p53 heterozygous mice: reduction of p53 dosage can promote cancer formation. EMBO J. 1998;17(16):4657–67.PubMed Venkatachalam S, Shi Y-P, Jones SN, Vogel H, Bradley A, Pinkel D, et al. Retention of wild-type p53 in tumors from p53 heterozygous mice: reduction of p53 dosage can promote cancer formation. EMBO J. 1998;17(16):4657–67.PubMed
106.
go back to reference Varley JM, Evans DG, Birch JM. Li-Fraumeni syndrome—a molecular and clinical review. Br J Cancer. 1997;1997(76):1–14. Varley JM, Evans DG, Birch JM. Li-Fraumeni syndrome—a molecular and clinical review. Br J Cancer. 1997;1997(76):1–14.
107.
go back to reference Alimonti A, Carracedo A, Clohessy JG, Trotman LC, Nardella C, Egia A, et al. Subtle variations in Pten dose determine cancer susceptibility. Nat Genet. 2010;42(5):454–8.PubMedCentralPubMed Alimonti A, Carracedo A, Clohessy JG, Trotman LC, Nardella C, Egia A, et al. Subtle variations in Pten dose determine cancer susceptibility. Nat Genet. 2010;42(5):454–8.PubMedCentralPubMed
108.
go back to reference Rusch VW, Venkatraman E. The importance of surgical staging in the treatment of malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 1996;111(4):815–26.PubMed Rusch VW, Venkatraman E. The importance of surgical staging in the treatment of malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 1996;111(4):815–26.PubMed
109.
go back to reference Bölükbasa S, Manegold C, Eberlein M, Bergmann T, Fisseler-Eckhoff A, Schirren J. Survival after trimodality therapy for malignant pleural mesothelioma: radical pleurectomy, chemotherapy with cisplatin/pemetrexed and radiotherapy. Lung Cancer. 2011;71(1):75–81. doi:10.1016/j.lungcan.2009.08.019. Bölükbasa S, Manegold C, Eberlein M, Bergmann T, Fisseler-Eckhoff A, Schirren J. Survival after trimodality therapy for malignant pleural mesothelioma: radical pleurectomy, chemotherapy with cisplatin/pemetrexed and radiotherapy. Lung Cancer. 2011;71(1):75–81. doi:10.​1016/​j.​lungcan.​2009.​08.​019.
112.
go back to reference Hazarika M, White Jr RM, Booth BP, Wang YC, Ham DY, Liang CY, et al. Pemetrexed in malignant pleural mesothelioma. Clin Cancer Res. 2005;11(3):982.PubMed Hazarika M, White Jr RM, Booth BP, Wang YC, Ham DY, Liang CY, et al. Pemetrexed in malignant pleural mesothelioma. Clin Cancer Res. 2005;11(3):982.PubMed
113.
go back to reference Berghmans T, Paesmans M, Lalami Y, Louviaux I, Luce S, Mascaux C. Activity of chemotherapy and immunotherapy on malignant mesothelioma: a systematic review of the literature with meta-analysis. Lung Cancer. 2002;38(2):111–21 (Amsterdam, Netherlands).PubMed Berghmans T, Paesmans M, Lalami Y, Louviaux I, Luce S, Mascaux C. Activity of chemotherapy and immunotherapy on malignant mesothelioma: a systematic review of the literature with meta-analysis. Lung Cancer. 2002;38(2):111–21 (Amsterdam, Netherlands).PubMed
114.
go back to reference Fizazi K, Ducreux M, Ruffié P, Bonnay M, Daniel C, Soria J-C, et al. Phase I, dose-finding, and pharmacokinetic study of raltitrexed combined with oxaliplatin in patients with advanced cancer. J Clin Oncol. 2000;18(11):2293–300.PubMed Fizazi K, Ducreux M, Ruffié P, Bonnay M, Daniel C, Soria J-C, et al. Phase I, dose-finding, and pharmacokinetic study of raltitrexed combined with oxaliplatin in patients with advanced cancer. J Clin Oncol. 2000;18(11):2293–300.PubMed
115.
go back to reference Fizazi K, Doubre H, Le Chevalier T, Riviere A, Viala J, Daniel C, et al. Combination of raltitrexed and oxaliplatin is an active regimen in malignant mesothelioma: results of a phase II study. J Clin Oncol. 2003;21(2):349–54. doi:10.1200/jco.2003.05.123.PubMed Fizazi K, Doubre H, Le Chevalier T, Riviere A, Viala J, Daniel C, et al. Combination of raltitrexed and oxaliplatin is an active regimen in malignant mesothelioma: results of a phase II study. J Clin Oncol. 2003;21(2):349–54. doi:10.​1200/​jco.​2003.​05.​123.PubMed
116.
go back to reference Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21(14):2636–44. doi:10.1200/jco.2003.11.136.PubMed Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21(14):2636–44. doi:10.​1200/​jco.​2003.​11.​136.PubMed
117.
go back to reference Karrison T, Kindler HL, Gandara DR, Lu C, Guterz TL, Nichols K, et al. Final analysis of a multi-center, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin (GC) plus bevacizumab (B) or placebo (P) in patients (pts) with malignant mesothelioma (MM). J Clin Oncol. 2007;25(18):5. (Suppl 18S Abstract 7526):391s. Karrison T, Kindler HL, Gandara DR, Lu C, Guterz TL, Nichols K, et al. Final analysis of a multi-center, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin (GC) plus bevacizumab (B) or placebo (P) in patients (pts) with malignant mesothelioma (MM). J Clin Oncol. 2007;25(18):5. (Suppl 18S Abstract 7526):391s.
118.
go back to reference Jänne PA, Taffaro ML, Salgia R, Johnson BE. Inhibition of epidermal growth factor receptor signaling in malignant pleural mesothelioma. Cancer Res. 2002;62(18):5242–7.PubMed Jänne PA, Taffaro ML, Salgia R, Johnson BE. Inhibition of epidermal growth factor receptor signaling in malignant pleural mesothelioma. Cancer Res. 2002;62(18):5242–7.PubMed
119.
go back to reference Govindan R, Kratzke RA, Herndon JE, Niehans GA, Vollmer R, Watson D, et al. Gefitinib in patients with malignant mesothelioma: a phase II study by the cancer and leukemia group B. Clin Cancer Res. 2005;11(6):2300–4. doi:10.1158/1078-0432.ccr-04-1940.PubMed Govindan R, Kratzke RA, Herndon JE, Niehans GA, Vollmer R, Watson D, et al. Gefitinib in patients with malignant mesothelioma: a phase II study by the cancer and leukemia group B. Clin Cancer Res. 2005;11(6):2300–4. doi:10.​1158/​1078-0432.​ccr-04-1940.PubMed
120.
go back to reference Jackman DM, Kindler HL, Yeap BY, Fidias P, Salgia R, Lucca J, et al. Erlotinib plus bevacizumab in previously treated patients with malignant pleural mesothelioma. Cancer. 2008;113(4):808–14. doi:10.1002/cncr.23617.PubMed Jackman DM, Kindler HL, Yeap BY, Fidias P, Salgia R, Lucca J, et al. Erlotinib plus bevacizumab in previously treated patients with malignant pleural mesothelioma. Cancer. 2008;113(4):808–14. doi:10.​1002/​cncr.​23617.PubMed
121.
go back to reference Rvd M, Robinson B, Nelson D. Gene therapy for malignant mesothelioma: beyond the infant years. Cancer Gene Ther. 2006;13(10):897–904. Rvd M, Robinson B, Nelson D. Gene therapy for malignant mesothelioma: beyond the infant years. Cancer Gene Ther. 2006;13(10):897–904.
122.
go back to reference Lindsay Y, McCoull D, Davidson L, Leslie NR, Fairservice A, Gray A, et al. Localization of agonist-sensitive PtdIns(3,4,5)P3 reveals a nuclear pool that is insensitive to PTEN expression. J Cell Sci. 2006;119(24):5160–8. doi:10.1242/jcs.000133.PubMed Lindsay Y, McCoull D, Davidson L, Leslie NR, Fairservice A, Gray A, et al. Localization of agonist-sensitive PtdIns(3,4,5)P3 reveals a nuclear pool that is insensitive to PTEN expression. J Cell Sci. 2006;119(24):5160–8. doi:10.​1242/​jcs.​000133.PubMed
Metadata
Title
The function, mechanisms, and role of the genes PTEN and TP53 and the effects of asbestos in the development of malignant mesothelioma: a review focused on the genes' molecular mechanisms
Authors
Leonardo Vinícius Monteiro de Assis
Mauro César Isoldi
Publication date
01-02-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 2/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1210-4

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