title: CIP2A mediates prostate cancer progression via the c-Myc signaling pathway.
abstract: Recent evidence suggests that cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that acts as a novel therapeutic target in a variety of tumors. In this study, we investigated the clinical significance of CIP2A and its function in our large collection of prostate samples. Between August 2000 and December 2013, 126 patients with histologically confirmed prostate cancer (PCa) and 92 with benign prostate hyperplasia (BPH) were recruited into the study. Quantitative real-time PCR (RT-PCR), Western blot, and immunohistochemistry analyses were used to quantify CIP2A expression in PCa clinical samples and cell lines. The relationships between CIP2A expression and clinicopathological features were analyzed. The functional role of CIP2A in PCa cells was evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation and invasion. High expression of CIP2A staining was 86.51 % (109/126) in 126 cases of PCa and 17.39 % (16/92) in 92 cases of BPH; the difference of CIP2A expression between PCa and BPH was statistically significant. CIP2A was significantly elevated in all five PCa cell lines when compared to the RWPE-1 cells at both the messenger RNA (mRNA) and protein levels. Silencing of CIP2A inhibited the proliferation of DU-145 cells which have a relatively high level of CIP2A in a time- and concentration-dependent manner, and the invasion and migration of DU-145 cells were distinctly suppressed. Furthermore, CIP2A knockdown led to substantial reductions in c-Myc levels in DU-145 cells, but no significant change in phosphorylated Akt expression after CIP2A knockdown in DU-145 cells. Our data suggest that the pathogenesis of human PCa maybe mediated by CIP2A, and CIP2A inhibition treatment may provide a promising strategy for the antitumor therapy of PCa, and thus, CIP2A could represent selective targets for the molecularly targeted treatments of PCa.
authors: Department of Urology, First Affiliated Hospital of Jinan University, No. 613 West Huangpu Dadao, Guangzhou, 510630, Guangdong, People's Republic of China.
authors: Zexiong
authors: Z
authors: Guo
authors: Dehao
authors: D
authors: Liu
authors: Zexuan
authors: Z
authors: Su
mesh_terms: D000368:Aged; D000818:Animals; D001324:Autoantigens / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D011470:Prostatic Hyperplasia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: D001324:Autoantigens; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; C489427:MYC protein, human; D008565:Membrane Proteins; D016271:Proto-Oncogene Proteins c-myc
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