Peptidyl-prolyl isomerase Pin1-mediated abrogation of APC-ß-catenin interaction in squamous cell carcinoma of cervix.

ABSTRACT

OBJECTIVE: The present study was aimed to investigate the importance of Pin1 expression in Squamous Cell Carcinoma (SCC) of cervix and to assess its level with ß-catenin and APC to understand the possible involvement of Pin1 in the regulation of these proteins and subsequent activation of Wnt/ß-catenin signaling. MATERIALS AND METHODS: Expression of Pin1, ß-catenin and APC was examined in 153 SCC patients by immunohistochemistry and revalidated by western blotting. RESULTS: Of the 153 SCC analyzed, Pin1 was overexpressed in 73 (47.71%) cases. Loss of membranous ß-catenin was noticed in 117 (76.47%) SCCs, whereas 66/153 (43.13%) and 93/153 (60.78%) cases showed its distinct cytoplasmic as well as nuclear accumulation respectively. Down regulation/loss of APC was observed in 69 (45.09%) cases, suggesting the activation of Wnt/ß-catenin pathway in SCCs. Pin1 showed the significant association with nuclear ß-catenin (r=.349, p<0.0001) and cytoplasmic loss of APC (r=-.287, p<0.0001). Both Pin1 as well as nuclear ß-catenin were found to be associated with tumor stage (p=0.004, p=0.031) and tumor size (p=0.022, p=0.003). The Pin1 overexpression showed the significant association with disease free survival (p=0.002) but not with overall survival (p=0.421) of SCC patients. CONCLUSION: Current results explore the expressional relationship between Pin1, ß-catenin and APC suggesting that Pin1 regulates the activation of Wnt/ß-catenin pathway in SCCs via modulating the interaction between ß-catenin and APC. Furthermore, the significant association of Pin1 and ß-catenin with tumor variables underscores the clinical utility of these proteins in cervical cancer.