Skip to main content
Top
Published in: Tumor Biology 12/2014

01-12-2014 | Research Article

CRTC2 and PROM1 expression in non-small cell lung cancer: analysis by Western blot and immunohistochemistry

Authors: Yalun Li, Yanqi He, Zhixin Qiu, Bin Zhou, Shaoqin Shi, Kui Zhang, Yangkun Luo, Qian Huang, Weimin Li

Published in: Tumor Biology | Issue 12/2014

Login to get access

Abstract

Accumulating evidence supports that genetic factors are another risk factors for lung cancer. Previously, we used whole exome sequencing with sanger sequencing to search for genetic-related mutations in one of four individuals from a pedigree with lung cancer history. Then, we used PCR-RFLP and direct-sequence in the sample size of 318 individuals with lung cancer (cases) and 272 controls. Recently, we detected two new genes including CRTC2 (CREB regulated transcription coactivator 2) and PROM1(human prominin-1,CD133). We investigated the CRTC2 mutation and PROM1 mutation of surgically resected NSCLC tissues (n=200). The presence or absence of CRTC2 and PROM1 mutation was analyzed by direct sequencing. The expression of CRTC2 and PROM1 was studied by western blot and immunohistochemical analysis of the lung cancer tissues which had the mutation of the two genes(cases), the samples without mutations(controls) and the normal lung tissue(controls). CRTC2 and PROM1 mutations in 5 NSCLC tissues and 3 NSCLC tissues out of the samples were identified. The positive results were closely correlated with clinicopathological features, such as male gender, adenocarcinoma, smoker status, and older age (≥55). We found that the CRTC2 and PROM1 expression were significantly higher in tissues of NSCLS with mutations than that without mutations and the normal lung tissue. The results imply that the high expression of CRTC2 and PROM1 may play an important role in the development and hereditary of NSCLC.
Literature
1.
go back to reference Alberg AJ, Brock MV, Samet JM. Epidemiology of lung cancer: looking to the future [J]. J Clin Oncol. 2005;23(14):3175–85.CrossRef Alberg AJ, Brock MV, Samet JM. Epidemiology of lung cancer: looking to the future [J]. J Clin Oncol. 2005;23(14):3175–85.CrossRef
2.
go back to reference Lichtenstein P, Holm NV, Verkasalo PK, et al. Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland [J]. N Engl J Med. 2000;343(2):78–85.CrossRef Lichtenstein P, Holm NV, Verkasalo PK, et al. Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland [J]. N Engl J Med. 2000;343(2):78–85.CrossRef
3.
go back to reference Hedges DJ, Burges D, Powell E, et al. Exome sequencing of a multigenerational human pedigree [J]. PLoS ONE. 2009;4(12):e8232.CrossRef Hedges DJ, Burges D, Powell E, et al. Exome sequencing of a multigenerational human pedigree [J]. PLoS ONE. 2009;4(12):e8232.CrossRef
4.
go back to reference He Y, Li Y, Qiu Z, et al. Identification and validation of PROM1 and CRTC2 mutations in lung cancer patients [J]. Mol Cancer. 2014;13(1):19.CrossRef He Y, Li Y, Qiu Z, et al. Identification and validation of PROM1 and CRTC2 mutations in lung cancer patients [J]. Mol Cancer. 2014;13(1):19.CrossRef
5.
go back to reference Koo SH, Flechner L, Qi L, et al. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism [J]. Nature. 2005;437(7062):1109–11.CrossRef Koo SH, Flechner L, Qi L, et al. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism [J]. Nature. 2005;437(7062):1109–11.CrossRef
6.
go back to reference Mizrak D, Brittan M, Alison M. CD133: molecule of the moment [J]. J Pathol. 2008;214(1):3–9.CrossRef Mizrak D, Brittan M, Alison M. CD133: molecule of the moment [J]. J Pathol. 2008;214(1):3–9.CrossRef
7.
go back to reference Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors [J]. Cancer Res. 2003;63(18):5821–8.PubMed Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors [J]. Cancer Res. 2003;63(18):5821–8.PubMed
8.
go back to reference Collins AT, Berry PA, Hyde C, et al. Prospective identification of tumorigenic prostate cancer stem cells [J]. Cancer Res. 2005;65(23):10946–51.CrossRef Collins AT, Berry PA, Hyde C, et al. Prospective identification of tumorigenic prostate cancer stem cells [J]. Cancer Res. 2005;65(23):10946–51.CrossRef
9.
go back to reference O’Brien CA, Pollett A, Gallinger S, et al. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice [J]. Nature. 2007;445(7123):106–10.CrossRef O’Brien CA, Pollett A, Gallinger S, et al. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice [J]. Nature. 2007;445(7123):106–10.CrossRef
10.
go back to reference Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al. Identification and expansion of human colon-cancer-initiating cells [J]. Nature. 2007;445(7123):111–5.CrossRef Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al. Identification and expansion of human colon-cancer-initiating cells [J]. Nature. 2007;445(7123):111–5.CrossRef
11.
go back to reference Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008 [J]. CA Cancer J Clin. 2008;58(2):71–96.CrossRef Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008 [J]. CA Cancer J Clin. 2008;58(2):71–96.CrossRef
12.
go back to reference Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002 [J]. CA Cancer J Clin. 2005;55(2):74–108.CrossRef Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002 [J]. CA Cancer J Clin. 2005;55(2):74–108.CrossRef
13.
go back to reference Sun S, Schiller JH, Gazdar AF. Lung cancer in never smokers—a different disease [J]. Nat Rev Cancer. 2007;7(10):778–90.CrossRef Sun S, Schiller JH, Gazdar AF. Lung cancer in never smokers—a different disease [J]. Nat Rev Cancer. 2007;7(10):778–90.CrossRef
14.
go back to reference Young RP, Hopkins RJ, Hay BA, et al. Lung cancer susceptibility model based on age, family history and genetic variants [J]. PLoS ONE. 2009;4(4):e5302.CrossRef Young RP, Hopkins RJ, Hay BA, et al. Lung cancer susceptibility model based on age, family history and genetic variants [J]. PLoS ONE. 2009;4(4):e5302.CrossRef
15.
go back to reference Gao Y, Goldstein AM, Consonni D, et al. Family history of cancer and nonmalignant lung diseases as risk factors for lung cancer [J]. Int J Cancer. 2009;125(1):146–52.CrossRef Gao Y, Goldstein AM, Consonni D, et al. Family history of cancer and nonmalignant lung diseases as risk factors for lung cancer [J]. Int J Cancer. 2009;125(1):146–52.CrossRef
16.
go back to reference Socinski MA, Bogart JA. Limited-stage small-cell lung cancer: the current status of combined-modality therapy [J]. J Clin Oncol. 2007;25(26):4137–45.CrossRef Socinski MA, Bogart JA. Limited-stage small-cell lung cancer: the current status of combined-modality therapy [J]. J Clin Oncol. 2007;25(26):4137–45.CrossRef
17.
go back to reference Bernstein ED, Herbert SM, Hanna NH. Chemotherapy and radiotherapy in the treatment of resectable non-small-cell lung cancer [J]. Ann Surg Oncol. 2006;13(3):291–301.CrossRef Bernstein ED, Herbert SM, Hanna NH. Chemotherapy and radiotherapy in the treatment of resectable non-small-cell lung cancer [J]. Ann Surg Oncol. 2006;13(3):291–301.CrossRef
18.
go back to reference Poleri C, Morero JL, Nieva B, et al. Risk of recurrence in patients with surgically resected stage I non-small cell lung carcinoma: histopathologic and immunohistochemical analysis [J]. Chest. 2003;123(6):1858–67.CrossRef Poleri C, Morero JL, Nieva B, et al. Risk of recurrence in patients with surgically resected stage I non-small cell lung carcinoma: histopathologic and immunohistochemical analysis [J]. Chest. 2003;123(6):1858–67.CrossRef
19.
go back to reference Screaton RA, Conkright MD, Katoh Y, et al. The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector [J]. Cell. 2004;119(1):61–74.CrossRef Screaton RA, Conkright MD, Katoh Y, et al. The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector [J]. Cell. 2004;119(1):61–74.CrossRef
20.
go back to reference Iourgenko V, Zhang W, Mickanin C, et al. Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells [J]. Proc Natl Acad Sci U S A. 2003;100(21):12147–52.CrossRef Iourgenko V, Zhang W, Mickanin C, et al. Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells [J]. Proc Natl Acad Sci U S A. 2003;100(21):12147–52.CrossRef
21.
go back to reference Dentin R, Liu Y, Koo SH, et al. Insulin modulates gluconeogenesis by inhibition of the coactivator TORC2 [J]. Nature. 2007;449(7160):366–9.CrossRef Dentin R, Liu Y, Koo SH, et al. Insulin modulates gluconeogenesis by inhibition of the coactivator TORC2 [J]. Nature. 2007;449(7160):366–9.CrossRef
22.
go back to reference Lerner RG, Depatie C, Rutter GA, et al. A role for the CREB co-activator CRTC2 in the hypothalamic mechanisms linking glucose sensing with gene regulation [J]. EMBO Rep. 2009;10(10):1175–81.CrossRef Lerner RG, Depatie C, Rutter GA, et al. A role for the CREB co-activator CRTC2 in the hypothalamic mechanisms linking glucose sensing with gene regulation [J]. EMBO Rep. 2009;10(10):1175–81.CrossRef
23.
go back to reference Fang WL, Lee MT, Wu LS, et al. CREB coactivator CRTC2/TORC2 and its regulator calcineurin crucially mediate follicle-stimulating hormone and transforming growth factor beta1 upregulation of steroidogenesis [J]. J Cell Physiol. 2012;227(6):2430–40.CrossRef Fang WL, Lee MT, Wu LS, et al. CREB coactivator CRTC2/TORC2 and its regulator calcineurin crucially mediate follicle-stimulating hormone and transforming growth factor beta1 upregulation of steroidogenesis [J]. J Cell Physiol. 2012;227(6):2430–40.CrossRef
24.
go back to reference Brown KA, Simpson ER. Obesity and breast cancer: progress to understanding the relationship [J]. Cancer Res. 2010;70(1):4–7.CrossRef Brown KA, Simpson ER. Obesity and breast cancer: progress to understanding the relationship [J]. Cancer Res. 2010;70(1):4–7.CrossRef
25.
go back to reference Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer [J]. Nat Rev Cancer. 2003;3(12):895–902.CrossRef Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer [J]. Nat Rev Cancer. 2003;3(12):895–902.CrossRef
26.
go back to reference Weigmann A, Corbeil D, Hellwig A, et al. Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells [J]. Proc Natl Acad Sci U S A. 1997;94(23):12425–30.CrossRef Weigmann A, Corbeil D, Hellwig A, et al. Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells [J]. Proc Natl Acad Sci U S A. 1997;94(23):12425–30.CrossRef
27.
go back to reference Miraglia S, Godfrey W, Yin AH, et al. A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning [J]. Blood. 1997;90(12):5013–21.CrossRef Miraglia S, Godfrey W, Yin AH, et al. A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning [J]. Blood. 1997;90(12):5013–21.CrossRef
28.
go back to reference Fargeas CA, Corbeil D, Huttner WB. AC133 antigen, CD133, prominin-1, prominin-2, etc.: prominin family gene products in need of a rational nomenclature [J]. Stem Cells. 2003;21(4):506–8.CrossRef Fargeas CA, Corbeil D, Huttner WB. AC133 antigen, CD133, prominin-1, prominin-2, etc.: prominin family gene products in need of a rational nomenclature [J]. Stem Cells. 2003;21(4):506–8.CrossRef
29.
go back to reference Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells [J]. Nature. 2004;432(7015):396–401.CrossRef Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells [J]. Nature. 2004;432(7015):396–401.CrossRef
30.
go back to reference Yin S, Li J, Hu C, et al. CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity [J]. Int J Cancer. 2007;120(7):1444–50.CrossRef Yin S, Li J, Hu C, et al. CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity [J]. Int J Cancer. 2007;120(7):1444–50.CrossRef
31.
go back to reference Olempska M, Eisenach PA, Ammerpohl O, et al. Detection of tumor stem cell markers in pancreatic carcinoma cell lines [J]. Hepatobiliary Pancreat Dis Int. 2007;6(1):92–7.PubMed Olempska M, Eisenach PA, Ammerpohl O, et al. Detection of tumor stem cell markers in pancreatic carcinoma cell lines [J]. Hepatobiliary Pancreat Dis Int. 2007;6(1):92–7.PubMed
32.
go back to reference Bruno S, Bussolati B, Grange C, et al. CD133+ renal progenitor cells contribute to tumor angiogenesis [J]. Am J Pathol. 2006;169(6):2223–35.CrossRef Bruno S, Bussolati B, Grange C, et al. CD133+ renal progenitor cells contribute to tumor angiogenesis [J]. Am J Pathol. 2006;169(6):2223–35.CrossRef
33.
go back to reference Rutella S, Bonanno G, Procoli A, et al. Cells with characteristics of cancer stem/progenitor cells express the CD133 antigen in human endometrial tumors [J]. Clin Cancer Res. 2009;15(13):4299–311.CrossRef Rutella S, Bonanno G, Procoli A, et al. Cells with characteristics of cancer stem/progenitor cells express the CD133 antigen in human endometrial tumors [J]. Clin Cancer Res. 2009;15(13):4299–311.CrossRef
34.
go back to reference Ferrandina G, Bonanno G, Pierelli L, et al. Expression of CD133-1 and CD133-2 in ovarian cancer [J]. Int J Gynecol Cancer. 2008;18(3):506–14.CrossRef Ferrandina G, Bonanno G, Pierelli L, et al. Expression of CD133-1 and CD133-2 in ovarian cancer [J]. Int J Gynecol Cancer. 2008;18(3):506–14.CrossRef
35.
go back to reference Monzani E, Facchetti F, Galmozzi E, et al. Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential [J]. Eur J Cancer. 2007;43(5):935–46.CrossRef Monzani E, Facchetti F, Galmozzi E, et al. Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential [J]. Eur J Cancer. 2007;43(5):935–46.CrossRef
36.
go back to reference Eramo A, Lotti F, Sette G, et al. Identification and expansion of the tumorigenic lung cancer stem cell population [J]. Cell Death Differ. 2008;15(3):504–14.CrossRef Eramo A, Lotti F, Sette G, et al. Identification and expansion of the tumorigenic lung cancer stem cell population [J]. Cell Death Differ. 2008;15(3):504–14.CrossRef
37.
go back to reference Maw MA, Corbeil D, Koch J, et al. A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration [J]. Hum Mol Genet. 2000;9(1):27–34.CrossRef Maw MA, Corbeil D, Koch J, et al. A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration [J]. Hum Mol Genet. 2000;9(1):27–34.CrossRef
38.
go back to reference Zhang Q, Zulfiqar F, Xiao X, et al. Severe retinitis pigmentosa mapped to 4p15 and associated with a novel mutation in the PROM1 gene [J]. Hum Genet. 2007;122(3–4):293–9.CrossRef Zhang Q, Zulfiqar F, Xiao X, et al. Severe retinitis pigmentosa mapped to 4p15 and associated with a novel mutation in the PROM1 gene [J]. Hum Genet. 2007;122(3–4):293–9.CrossRef
39.
go back to reference Rappa G, Fodstad O, Lorico A. The stem cell-associated antigen CD133 (Prominin-1) is a molecular therapeutic target for metastatic melanoma [J]. Stem Cells. 2008;26(12):3008–17.CrossRef Rappa G, Fodstad O, Lorico A. The stem cell-associated antigen CD133 (Prominin-1) is a molecular therapeutic target for metastatic melanoma [J]. Stem Cells. 2008;26(12):3008–17.CrossRef
Metadata
Title
CRTC2 and PROM1 expression in non-small cell lung cancer: analysis by Western blot and immunohistochemistry
Authors
Yalun Li
Yanqi He
Zhixin Qiu
Bin Zhou
Shaoqin Shi
Kui Zhang
Yangkun Luo
Qian Huang
Weimin Li
Publication date
01-12-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 12/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2011-0

Other articles of this Issue 12/2014

Tumor Biology 12/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine