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01-03-2011 | Translational Research and Biomarkers

CIP2A is Overexpressed in Non-Small Cell Lung Cancer and Correlates with Poor Prognosis

Authors: Qian-Ze Dong, MD, PhD, Yang Wang, MD, PhD, Xin-Jun Dong, MASc, Zi-Xuan Li, PhD, Zhong-Ping Tang, MD, Quan-Ze Cui, MD, En-Hua Wang, MD

Published in: Annals of Surgical Oncology | Issue 3/2011

Abstract

Background

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein inhibiting proteolytic degradation of c-MYC. In this study, we investigated the clinical relevance of CIP2A in NSCLC.

Materials and Methods

We analyzed CIP2A mRNA expression in 29 NSCLC tissues using quantitative reverse transcription polymerase chain reaction (RT-QPCR). We also examined the expression of CIP2A protein by immunohistochemistry in 90 lung cancer specimens and correlated its expression with c-MYC expression and clinicopathological parameters. The functional roles of CIP2A in lung cancer cell lines were evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation and invasion.

Results

In 29 lung cancer tissues examined, 24 of them (82.7%) exhibited much stronger levels of CIP2A mRNA compared with their corresponding normal tissues. Moreover, CIP2A mRNA expression levels correlated with c-MYC mRNA levels. Furthermore, CIP2A protein was found to be overexpressed in 72.2% of 90 human lung cancer samples and correlated with poor survival (P < 0.05). In addition, the CIP2A status was a significant prognostic factor for NSCLC patients (P = 0.0136). Depleting CIP2A expression inhibited growth and clonogenic potential in lung cancer cell lines.

Conclusions

CIP2A is an oncoprotein overexpressed in NSCLC, and its expression is associated with poor prognosis and malignant cell proliferation.

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Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. BMJ. 1995;311:899–909.

O’Mahony D, Kummar S, Gutierrez ME. Non-small-cell lung cancer vaccine therapy: a concise review. J Clin Oncol. 2005;23:9022–8.PubMedCrossRef

Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123–32.PubMedCrossRef

Tsao MS, Sakurada A, Cutz JC, Zhu CQ, Kamel-Reid S, Squire J, et al. Erlotinib in lung cancer—molecular and clinical predictors of outcome. N Engl J Med. 2005;353:133–44.PubMedCrossRef

Zhang YA, Nemunaitis J, Samuel SK, Chen P, Shen Y, Tong AW. Antitumor activity of an oncolytic adenovirus-delivered oncogene small interfering RNA. Cancer Res. 2006;66:9736–43.PubMedCrossRef

Junttila MR, Puustinen P, Niemelä M, Ahola R, Arnold H, Böttzauw T, et al. CIP2A inhibits PP2A in human malignancies. Cell. 2007;130:51–62.PubMedCrossRef

Khanna A, Böckelman C, Hemmes A, Junttila MR, Wiksten JP, Lundin M, et al. MYC-dependent regulation and prognostic role of CIP2A in gastric cancer. J Natl Cancer Inst. 2009;101:793–805.PubMedCrossRef

Li W, Ge Z, Liu C, Liu Z, Björkholm M, Jia J, et al. CIP2A is overexpressed in gastric cancer and its depletion leads to impaired clonogenicity, senescence, or differentiation of tumor cells. Clin Cancer Res. 2008;14:3722–8.PubMedCrossRef

Côme C, Laine A, Chanrion M, Edgren H, Mattila E, Liu X, et al. CIP2A is associated with human breast cancer aggressivity. Clin Cancer Res. 2009;15:5092–100.PubMedCrossRef

10.

Burke L, Flieder DB, Guinee DG, Brambilla E, Freedman AN, Bennet WP, et al. Prognostic implications of molecular and immunohistochemical profiles of the Rb and p53 cell cycle regulatory pathways in primary non-small cell lung carcinoma. Clin Cancer Res. 2005;11:232–41.PubMed

11.

Arnold HK, Sears RC. A tumor suppressor role for PP2A-B56alpha through negative regulation of c-Myc and other key oncoproteins. Cancer Metastasis Rev. 2008;27:147–58.PubMedCrossRef

12.

Junttila MR, Westermarck J. Mechanisms of MYC stabilization in human malignancies. Cell Cycle. 2008;7:592–6.PubMedCrossRef

13.

Sears RC. The life cycle of C-myc: from synthesis to degradation. Cell Cycle. 2004;3:1133–7.PubMedCrossRef

14.

Yeh E, Cunningham M, Arnold H, Chasse D, Monteith T, Ivaldi G, et al. A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells. Nat Cell Biol. 2004;6:308–18.PubMedCrossRef

15.

Dang CV, Resar LM, Emison E, Kim S, Li Q, Prescott JE, et al. Function of the c-Myc oncogenic transcription factor. Exp Cell Res. 1999;253:63–77.PubMedCrossRef

16.

Volm M, Koomagi R. Prognostic relevance of c-Myc and caspase-3 for patients with non-small cell lung cancer. Oncol Rep. 2000;7:95–8.PubMed

17.

Yang G, Timme TL, Frolov A, Wheeler TM, Thompson TC. Combined c-Myc and caveolin-1 expression in human prostate carcinoma predicts prostate carcinoma progression. Cancer. 2005;103:1186–94.PubMedCrossRef

18.

Qian J, Hirasawa K, Bostwick DG, Bergstralh EJ, Slezak JM, Anderl KL, et al., Loss of p53 and c-myc overrepresentation in stage T(2–3)N(1–3)M(0) prostate cancer are potential markers for cancer progression. Mod Pathol. 2002;15:35–44.PubMedCrossRef

19.

Sharrard RM, Royds JA, Rogers S, Shorthouse AJ. Patterns of methylation of the c-myc gene in human colorectal cancer progression. Br J Cancer. 1992;65:667–72.PubMedCrossRef

20.

Watson PH, Safneck JR, Le K, Dubik D, Shiu RP. Relationship of c-myc amplification to progression of breast cancer from in situ to invasive tumor and lymph node metastasis. J Natl Cancer Inst. 1993;85:902–7.PubMedCrossRef

21.

Huang CL, Liu D, Ishikawa S, Nakashima T, Nakashima N, Yokomise H, et al. Wnt1 overexpression promotes tumour progression in non-small cell lung cancer. Eur J Cancer. 2008;44:2680–8.PubMedCrossRef

Title: CIP2A is Overexpressed in Non-Small Cell Lung Cancer and Correlates with Poor Prognosis
Authors: Qian-Ze Dong, MD, PhD
Yang Wang, MD, PhD
Xin-Jun Dong, MASc
Zi-Xuan Li, PhD
Zhong-Ping Tang, MD
Quan-Ze Cui, MD
En-Hua Wang, MD
Publication date: 01-03-2011
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 3/2011
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-010-1313-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

CIP2A is Overexpressed in Non-Small Cell Lung Cancer and Correlates with Poor Prognosis

Abstract

Background

Materials and Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Materials and Methods

Results

Conclusions

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