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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Acknowledgment
This work was supported by grants from the National Natural Science Foundation of China (No. 30470764 and No. 30670917 to En-Hua Wang, No. 30670888 to Chen Zhao).
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10434_2010_1313_MOESM1_ESM.pdf
Supplement Figure 1 A Real-time PCR analyses of CIP2A depletion efficiency in HBE cells. B MTT assay was performed after CIP2A siRNA treatment in HBE cells. A slight reduction of absorbance was observed. C and D Assessment of clonogenic potentials of the CIP2A siRNA treated HBE cells. Number of colonies was counted. The number of colonies formed by cells treated with CIP2A siRNA (138 ± 23, mean ± SD) was comparable with that of control cells (165 ± 12, mean ± SD) (P = 0.159). (PDF 49 kb)
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Dong, QZ., Wang, Y., Dong, XJ. et al. CIP2A is Overexpressed in Non-Small Cell Lung Cancer and Correlates with Poor Prognosis. Ann Surg Oncol 18, 857–865 (2011). https://doi.org/10.1245/s10434-010-1313-8
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DOI: https://doi.org/10.1245/s10434-010-1313-8