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Published in: Journal of Cancer Research and Clinical Oncology 3/2008

01-03-2008 | Original Paper

Nuclear to cytoplasmic shift of p33ING1b protein from normal oral mucosa to oral squamous cell carcinoma in relation to clinicopathological variables

Authors: Jin-Ting Zhang, Da-Wei Wang, Qing-Xing Li, Zhen-Long Zhu, Ming-Wei Wang, Dong-Sheng Cui, Yan-Hong Yang, Yu-Xin Gu, Xiao-Feng Sun

Published in: Journal of Cancer Research and Clinical Oncology | Issue 3/2008

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Abstract

Purpose

p33ING1b, as a candidate tumour suppressor gene, has been found to be expressed a proportion of oral squamous cell carcinomas (OSCCs), however, its clinicopathological significance is not studied yet. Our aim was to investigate association of p33ING1b expression with clinicopathological variables and particularly interesting new cysteine–histidine rich protein (PINCH) in OSCCs.

Methods

p33ING1b expression was immumohistochemically examined in 20 normal oral mucosa specimens and 49 OSCCs.

Results

Normal squamous cells showed only p33ING1b nuclear expression (no cytoplasmic expression), with a rate of 90% positive cases. While 24% of OSCCs appeared cytoplasmic expression (11 of them with weak nuclear staining) and the rest tumours (76%) were negative for p33ING1b. Furthermore, the cases having lymph node metastasis showed a higher frequency of positive cytoplasmic expression than those without metastasis (P = 0.03). The p33ING1b cytoplasmic expression was positively related to PINCH expression (P = 0.04), the cases positive for both proteins had a high rate of the metastasis (P = 0.03).

Conclusions

The transfer of p33ING1b protein from the nucleus to the cytoplasm may result in loss of normal cellular function of the protein, which might play a role in the tumourigenesis and metastasis of OSCCs.
Literature
go back to reference Bosari S, Viale G, Bossi P, Maggioni M, Coggi G, Murray J, Lee AK (1994) Cytoplasmic accumulation of p53 protein: an independent prognostic indicator in colorectal adenocarcinomas. J Natl Cancer Inst 86:681–687PubMedCrossRef Bosari S, Viale G, Bossi P, Maggioni M, Coggi G, Murray J, Lee AK (1994) Cytoplasmic accumulation of p53 protein: an independent prognostic indicator in colorectal adenocarcinomas. J Natl Cancer Inst 86:681–687PubMedCrossRef
go back to reference Chen L, Lu W, Agrawal S, Zhou W, Zhang R, Chen J (1999) Ubiquitous induction of p53 in tumor cells by antisense inhibition of MDM2 expression. Mol Med 5:21–34PubMed Chen L, Lu W, Agrawal S, Zhou W, Zhang R, Chen J (1999) Ubiquitous induction of p53 in tumor cells by antisense inhibition of MDM2 expression. Mol Med 5:21–34PubMed
go back to reference Flamini G, Curigliano G, Ratto C, Astone A, Ferretti G, Nucera P, Sofo L, Sgambato A, Boninsegna A, Crucitti F, Cittadini A (1996) Prognostic significance of cytoplasmic p53 overexpression in colorectal cancer. An immunohistochemical analysis. Eur J Cancer 32:802–806CrossRef Flamini G, Curigliano G, Ratto C, Astone A, Ferretti G, Nucera P, Sofo L, Sgambato A, Boninsegna A, Crucitti F, Cittadini A (1996) Prognostic significance of cytoplasmic p53 overexpression in colorectal cancer. An immunohistochemical analysis. Eur J Cancer 32:802–806CrossRef
go back to reference Gao J, Arbman G, Reader A, Sun XF (2004) Expression of PINCH protein is an independent factor in colorectal cancer patients. Neoplasia 6:796–801PubMedCrossRef Gao J, Arbman G, Reader A, Sun XF (2004) Expression of PINCH protein is an independent factor in colorectal cancer patients. Neoplasia 6:796–801PubMedCrossRef
go back to reference Garkavtsev I, Kazarov A, Gudkov A, Riabowol K (1996) Suppression of the novel growth inhibitor p33ING1 promotes neoplastic transformation. Nat Genet 14:415–420PubMedCrossRef Garkavtsev I, Kazarov A, Gudkov A, Riabowol K (1996) Suppression of the novel growth inhibitor p33ING1 promotes neoplastic transformation. Nat Genet 14:415–420PubMedCrossRef
go back to reference Garkavtsev I, Grigorian IA, Ossovskaya VS, Chernov M V, Chumakov P M, Gudkov A V (1998) The candidate tumour suppressor p33ING1 cooperates with p53 in cell growth control. Nature 391:295–298PubMedCrossRef Garkavtsev I, Grigorian IA, Ossovskaya VS, Chernov M V, Chumakov P M, Gudkov A V (1998) The candidate tumour suppressor p33ING1 cooperates with p53 in cell growth control. Nature 391:295–298PubMedCrossRef
go back to reference Gunduz M, Ouchida M, Fukushima K, Hanafusa H, Etani T, Nishioka S, Nishizaki K, Shimizu K (2000) Genomic structure of the human ING1 gene and tumor-specific mutations detected in head and neck squamous cell carcinomas. Cancer Res 60:3143–3146PubMed Gunduz M, Ouchida M, Fukushima K, Hanafusa H, Etani T, Nishioka S, Nishizaki K, Shimizu K (2000) Genomic structure of the human ING1 gene and tumor-specific mutations detected in head and neck squamous cell carcinomas. Cancer Res 60:3143–3146PubMed
go back to reference Gunduz M, Nagatsuka H, Demircan K, Gunduz E, Cengiz B, Ouchida M, Tsujigiwa H, Yamachika E, Fukushima K, Beder L, Hirohata S, Ninomiya Y, Nishizaki K, Shimizu K, Nagai N (2005) Frequent deletion and down-regulation of ING4, a candidate tumor suppressor gene at 12p13, in head and neck squamous cell carcinomas. Gene 356:109–117PubMedCrossRef Gunduz M, Nagatsuka H, Demircan K, Gunduz E, Cengiz B, Ouchida M, Tsujigiwa H, Yamachika E, Fukushima K, Beder L, Hirohata S, Ninomiya Y, Nishizaki K, Shimizu K, Nagai N (2005) Frequent deletion and down-regulation of ING4, a candidate tumor suppressor gene at 12p13, in head and neck squamous cell carcinomas. Gene 356:109–117PubMedCrossRef
go back to reference Hoque MO, Kawamata H, Nakashiro K, Omotehara F, Hino S, Uchida D, Harada K, Begum NM, Yoshida H, Sato M, Fujimori T (2002) Dysfunction of the p53 tumor suppressor pathway in head and neck cancer. Int J Oncol 21:119–126PubMed Hoque MO, Kawamata H, Nakashiro K, Omotehara F, Hino S, Uchida D, Harada K, Begum NM, Yoshida H, Sato M, Fujimori T (2002) Dysfunction of the p53 tumor suppressor pathway in head and neck cancer. Int J Oncol 21:119–126PubMed
go back to reference Klotzsche O, Etzrodt D, Hohenberg H, Bohn W, Deppert W (1998) Cytoplasmic retention of mutant tsp53 is dependent on an intermediate filament protein (vimentin) scaffold. Oncogene 16:3423–3434PubMedCrossRef Klotzsche O, Etzrodt D, Hohenberg H, Bohn W, Deppert W (1998) Cytoplasmic retention of mutant tsp53 is dependent on an intermediate filament protein (vimentin) scaffold. Oncogene 16:3423–3434PubMedCrossRef
go back to reference Krishnamurthy J, Kannan K, Feng J, Mohanprasad BK, Tsuchida N, Shanmugam G (2001) Mutational analysis of the candidate tumor suppressor gene ING1 in Indian oral squamous cell carcinoma. Oral Oncol 37:222–224PubMedCrossRef Krishnamurthy J, Kannan K, Feng J, Mohanprasad BK, Tsuchida N, Shanmugam G (2001) Mutational analysis of the candidate tumor suppressor gene ING1 in Indian oral squamous cell carcinoma. Oral Oncol 37:222–224PubMedCrossRef
go back to reference Nouman GS, Anderson JJ, Lunec J, Angus B (2003) The role of the tumour suppressor p33 ING1b in human neoplasia. J Clin Pathol 56:491–496PubMedCrossRef Nouman GS, Anderson JJ, Lunec J, Angus B (2003) The role of the tumour suppressor p33 ING1b in human neoplasia. J Clin Pathol 56:491–496PubMedCrossRef
go back to reference Nouman GS, Anderson JJ, Mathers ME, Leonard N, Crosier S, Lunec J, Angus B (2002a) Nuclear to cytoplasmic compartment shift of the p33ING1b tumour suppressor protein is associated with malignancy in melanocytic lesions. Histopathology 40:360–366PubMedCrossRef Nouman GS, Anderson JJ, Mathers ME, Leonard N, Crosier S, Lunec J, Angus B (2002a) Nuclear to cytoplasmic compartment shift of the p33ING1b tumour suppressor protein is associated with malignancy in melanocytic lesions. Histopathology 40:360–366PubMedCrossRef
go back to reference Nouman GS, Anderson JJ, Wood KM, Lunec J, Hall AG, Reid MM, Angus B (2002b) Loss of nuclear expression of the inhibitor of growth p33ING1b in childhood acute lymphoblastic leukaemia. J Clin Pathol 55:596–601PubMedCrossRef Nouman GS, Anderson JJ, Wood KM, Lunec J, Hall AG, Reid MM, Angus B (2002b) Loss of nuclear expression of the inhibitor of growth p33ING1b in childhood acute lymphoblastic leukaemia. J Clin Pathol 55:596–601PubMedCrossRef
go back to reference Ohgi T, Masaki T, Nakai S, Morishita A, Yukimasa S, Nagai M, Miyauchi Y, Funaki T, Kurokohchi K, Watanabe S, Kuriyama S (2002) Expression of p33(ING1) in hepatocellular carcinoma: relationships to tumour differentiation and cyclin E kinase activity. Scand J Gastroenterol 37:1440–1448PubMedCrossRef Ohgi T, Masaki T, Nakai S, Morishita A, Yukimasa S, Nagai M, Miyauchi Y, Funaki T, Kurokohchi K, Watanabe S, Kuriyama S (2002) Expression of p33(ING1) in hepatocellular carcinoma: relationships to tumour differentiation and cyclin E kinase activity. Scand J Gastroenterol 37:1440–1448PubMedCrossRef
go back to reference Oki E, Maehara Y, Tokunaga E, Kakeji Y, Sugimachi K (1999) Reduced expression of p33(ING1) and the relationship with p53 expression in human gastric cancer. Cancer Lett 147:157–162PubMedCrossRef Oki E, Maehara Y, Tokunaga E, Kakeji Y, Sugimachi K (1999) Reduced expression of p33(ING1) and the relationship with p53 expression in human gastric cancer. Cancer Lett 147:157–162PubMedCrossRef
go back to reference Rearden A (1994) A new LIM protein containing an autopitope homologous to “senescent cell antigen”. Biochem Biophys Res Commun 201:1124–1134PubMedCrossRef Rearden A (1994) A new LIM protein containing an autopitope homologous to “senescent cell antigen”. Biochem Biophys Res Commun 201:1124–1134PubMedCrossRef
go back to reference Scott M, Bonnefin P, Vieyra D, Boisvert FM, Young D, Bazett-Jones DP, Riabowol K (2001) UV-induced binding of ING1 to PCNA regulates the induction of apoptosis. J Cell Sci 114:3455–3462PubMed Scott M, Bonnefin P, Vieyra D, Boisvert FM, Young D, Bazett-Jones DP, Riabowol K (2001) UV-induced binding of ING1 to PCNA regulates the induction of apoptosis. J Cell Sci 114:3455–3462PubMed
go back to reference Sun XF, Carstensen JM, Zhang H, Stal O, Wingren S, Hatschek T, Nordenskjold B (1992) Prognostic significance of cytoplasmic p53 oncoprotein in colorectal adenocarcinoma. Lancet 340:1369–1373PubMedCrossRef Sun XF, Carstensen JM, Zhang H, Stal O, Wingren S, Hatschek T, Nordenskjold B (1992) Prognostic significance of cytoplasmic p53 oncoprotein in colorectal adenocarcinoma. Lancet 340:1369–1373PubMedCrossRef
go back to reference Sun XF, Zhang H, Carstensen J, Jansson A, Nordenskjold B (1997) Heat shock protein 72/73 in relation to cytoplasmic p53 expression and prognosis in colorectal adenocarcinomas. Int J Cancer 74:600–604PubMedCrossRef Sun XF, Zhang H, Carstensen J, Jansson A, Nordenskjold B (1997) Heat shock protein 72/73 in relation to cytoplasmic p53 expression and prognosis in colorectal adenocarcinomas. Int J Cancer 74:600–604PubMedCrossRef
go back to reference Tachibana M, Shinagawa Y, Kawamata H, Omotehara F, Horiuchi H, Ohkura Y, Kubota K, Imai Y, Fujibayashi T, Fujimori T (2002) RT-PCR amplification of RNA extracted from formalin-fixed, paraffin-embedded oral cancer sections: analysis of p53 pathway. Anticancer Res 23:2891–2896 Tachibana M, Shinagawa Y, Kawamata H, Omotehara F, Horiuchi H, Ohkura Y, Kubota K, Imai Y, Fujibayashi T, Fujimori T (2002) RT-PCR amplification of RNA extracted from formalin-fixed, paraffin-embedded oral cancer sections: analysis of p53 pathway. Anticancer Res 23:2891–2896
go back to reference Tao W, Levine AJ (1999) Nucleocytoplasmic shuttling of oncoprotein Hdm-2 is required for Hdm2-mediated degradation of p53. Proc Natl Acad Sci USA 96:3077–3080PubMedCrossRef Tao W, Levine AJ (1999) Nucleocytoplasmic shuttling of oncoprotein Hdm-2 is required for Hdm2-mediated degradation of p53. Proc Natl Acad Sci USA 96:3077–3080PubMedCrossRef
go back to reference Toyama T, Iwase H, Watson P, Muzik H, Saettler E, Magliocco A, DiFrancesco L, Forsyth P, Garkavtsev I, Kobayashi S, Riabowol K (1999) Suppression of ING1 expression in sporadic breast cancer. Oncogene 8:5187–5193CrossRef Toyama T, Iwase H, Watson P, Muzik H, Saettler E, Magliocco A, DiFrancesco L, Forsyth P, Garkavtsev I, Kobayashi S, Riabowol K (1999) Suppression of ING1 expression in sporadic breast cancer. Oncogene 8:5187–5193CrossRef
go back to reference Tu Y, Li F,Giocoechea S, Wu C (1999) The LIM-only protein PINCH directly interacts with intergrin-linked kinase and is recruited to inegrin-rich sites in spreading cells. Mol Cell Biol 19:2425–2434PubMed Tu Y, Li F,Giocoechea S, Wu C (1999) The LIM-only protein PINCH directly interacts with intergrin-linked kinase and is recruited to inegrin-rich sites in spreading cells. Mol Cell Biol 19:2425–2434PubMed
go back to reference Vieyra D, Senger DL, Toyama T, Muzik H, Brasher PM, Johnston RN, Riabowol K, Forsyth PA (2003) Altered subcellular localization and low frequency of mutations of ING1 in human brain tumors. Clin Cancer Res 9:5952–5961PubMed Vieyra D, Senger DL, Toyama T, Muzik H, Brasher PM, Johnston RN, Riabowol K, Forsyth PA (2003) Altered subcellular localization and low frequency of mutations of ING1 in human brain tumors. Clin Cancer Res 9:5952–5961PubMed
go back to reference Wang-Rodriguez J, Dreilinger AD, Alsharabi GM, Rearden A (2002) The signaling adapter protein is up-regulated in he stroma of common cancess, notably at invasive edges. Cancer 95:1387–1395PubMedCrossRef Wang-Rodriguez J, Dreilinger AD, Alsharabi GM, Rearden A (2002) The signaling adapter protein is up-regulated in he stroma of common cancess, notably at invasive edges. Cancer 95:1387–1395PubMedCrossRef
go back to reference Zhang JT, Li QX, Wang DW, Zhu ZL, Yang YH, Cui DS, Wang MW, Sun XF (2005) Up regulation of PINCH in the stroma of oral squamous cell carcinoma predicts nodal metastasis. Oncol Rep 14:1519–1522PubMed Zhang JT, Li QX, Wang DW, Zhu ZL, Yang YH, Cui DS, Wang MW, Sun XF (2005) Up regulation of PINCH in the stroma of oral squamous cell carcinoma predicts nodal metastasis. Oncol Rep 14:1519–1522PubMed
Metadata
Title
Nuclear to cytoplasmic shift of p33ING1b protein from normal oral mucosa to oral squamous cell carcinoma in relation to clinicopathological variables
Authors
Jin-Ting Zhang
Da-Wei Wang
Qing-Xing Li
Zhen-Long Zhu
Ming-Wei Wang
Dong-Sheng Cui
Yan-Hong Yang
Yu-Xin Gu
Xiao-Feng Sun
Publication date
01-03-2008
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 3/2008
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-007-0305-y

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