Clinical significance of inactivated glycogen synthase kinase 3ß in HPV-associated cervical cancer: Relationship with Wnt/ß-catenin pathway activation.

ABSTRACT

PROBLEM: To determine the role of inactivated GSK3ß with respect to Wnt/ß-catenin pathway activation in HPV-16/18-associated cervical cancer. METHOD OF STUDY The expression of active (pGSK3ß-Try(216)), inactive (pGSK3ß-Ser(9)), and c-Myc as well as HPV-16/18 infection was analyzed in cervical intra-epithelial neoplasia (CIN), squamous cell carcinoma (SCCs) and normal by immunohistochemistry and multiplex PCR. The proteins level was also compared with ß-catenin and APC expression. RESULTS: The dramatic decrease of pGSK3ß-Try(216) expression but ectopic overexpression of pGSK3ß-Ser(9) and c-Myc was observed both in CIN and SCCs samples compared to normal tissues. 57/67 CIN and 132/153 SCCs showed HPV-16 infection, while 3/67 CIN and 4/153 SCCs were harbored with HPV-18 infection. Both the proteins were significantly upregulated in HPV-16 infected cases (P = 0.0001; P = 0.001) and also positively correlated with nuclear ß-catenin (P = 0.0001; P = 0.0001). CONCLUSION: The process of generation of HPV-16-associated cervical tumorigenesis is synergized with GSK3ß inactivation and overactivation of Wnt/ß-catenin pathway.