Significance of Wnt B catenin Signaling Pathway in the Pathogenesis of Cervical Cancer

Abstract

Background: Cervical cancer is one of the aggressive gynaecologic malignancies newlineaccounting for higher rate of morbidity and mortality in India. The infection of highrisk newlinehuman papilloma virus (HR-HPV) has been considered as the prime cause for newlinethis dreaded disease. In addition to this, the abrogated cellular signalings also newlinecontribute as co-factor during neoplastic transformation of cervix cell. Amongst newlinevarious other signalings, canonical Wnt/and#946;-catenin pathway is considered as the newlinehallmark transducer for several human cancers. But its oncogenic role in HPV newlineassociated cervical neoplasia is still not been completely comprehended. Therefore, newlinethe present study was aimed to determine the biological and clinical relevance of newlinemajor components of Wnt/and#946;-catenin pathway in the pathogenesis of cervical cancer as newlinewell as to investigate the possible molecular impact of HPV-16/-18 on their newlineregulation. newlineMaterials and Methods: The expression of Wnt/and#946;-catenin pathway proteins newline[Dishevelled-1 (Dvl-1), Pin-1, Adenomatosis Polyposis coli (APC), Glycogen newlineSynthase kinase-3and#946; (GSK3and#946;), and#946;-catenin, Cyclin D1, c-Myc and cyclooxygenase-2 newline(Cox-2)] analyzed in 67 cervical intraepithelial neoplasia (CIN), 174 invasive cervical newlinecarcinoma (ICCs) and 100 normal patients by immunohistochemistry as well as newlinerevalidated by Western Blotting. The multiplex PCR amplification was carried out for newlineHPV-16 and HPV-18 genotyping. The protein levels were further correlated with newlineclinicopathological parameters of patients as well as with HPV infection. In addition, newlinethe expression of other cellular proteins like p53/p21, E-cadherin, AKT and newlineInterleukin-10 (IL-10) as well as their association with HPV-E6 were also examined. newlineResults: On the IHC analysis, the cytoplasmic over-expression of transducer protein, newlineDvl-1 was detected in 31.3% of CIN and 29.8% of ICCs while, 53.7% of CIN and newline54.5% of ICCs showed its nuclear up-regulation. The increased cytoplasmic/nuclear newlinepositivity of Wnt co-activator, Pin-1 was noted in 73.1% of CIN and 51.7% of ICCs. newlineThere was dramatic ...