Downregulation of nuclear and cytoplasmic Chibby is associated with advanced cervical cancer

Chibby has been identified as a putative tumor suppressor and antagonist to β-catenin, thereby controlling the Wnt signaling pathway. Chibby is typically downregulated in numerous types of cancer and may be associated with tumorigenesis. The present study aimed at clarifying the following: i) Whether Chibby antagonizes β-catenin in cervical cancer; ii) whether Chibby and β-catenin mRNA expression is associated with cancer progression; and iii) whether Chibby and β-catenin expression may be used as a biomarker. A total of 87 paraffin-embedded cervical sections with distinct cervical intraepithelial neoplasia (CIN) stages (chronic cervicitis, CIN 1, CIN 2, CIN 3 and invasive squamous cell carcinoma) were collected between June 2004 and October 2012 The mRNA expression level of Chibby and β-catenin was determined using the polymerase chain reaction. Protein expression and cellular localization of Chibby and β-catenin were determined using immunohistochemistry. Chibby and β-catenin were analyzed for possible association with the progression of cervical cancer. Chibby mRNA expression and the Chibby/β-catenin ratio were identified to be downregulated in invasive tumors. Positive cytoplasmic and nuclear staining for Chibby was associated with CIN staging and decreased as the CIN stage increased. In addition, the cytoplasmic and membrane intensity of β-catenin was associated with invasive tumors, in which a significantly increased level of protein expression was detected. Chibby may be a tumor suppressor in cervical cancer, since the dysregulation of Chibby expression is associated with tumorigenesis in cervical cancer. Chibby and β-catenin expression together may potentially to a biomarker for disease progression in cervical cancer.