Differential expression of cadherins and catenins in gynecological cancers

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Objective: Gynecological malignancies such as cervical and ovarian cancer are a major health issue in women. The overall survival and mortality rates of gynecological cancer patients may significantly improve if the cancer is diagnosed at the pre-neoplastic or early neoplastic lesion stages. Cadherin-catenin complex of proteins play a major role in cell adhesion and proliferation. Cadherin and catenin dysregulation is strongly associated with breast and prostate cancer progression and metastasis. However, a cohesive expression profile of these molecules in gynecological cancers is not well defined. In the present study, we determine the collective expression profile of cadherins and catenins in gynecological cancers.

Materials and methods: Tissue micro array slides were used to avoid sample to sample variation during processing. AccuMax gynecological cancer tissue micro array slides containing 100 tissue spots with cancers and corresponding normal tissues were used to study expression profile of E-cadherin, P-cadherin, N-cadherin, β-catenin, and plakoglobin with immunohistochemical techniques using Vector Elite ABC kit. RIPA extracts were made of cervical cancer cell lines (SiHa, Caski, HeLa, C33-A) and ovarian cancer cell lines (SKOV-3, OVCAR-3, CaOV-3, PA-1). Equal amount of proteins were resolved by SDS-PAGE, and immunoblotted with E (4A2), P (6A9), N (13A9)-cadherins, β-catenin (5H10) and plakoglobin (PG5.1) specific monoclonal antibodies.

Results: We observed the progressive down regulation of E and P-cadherin in cervical intraepithelial neoplasia (CIN), invasive squamous cell carcinoma (SCC) and mucinous adenocarcinoma compared to normal cervix. N-cadherin was not present in normal cervix and CIN cases however it was present in invasive SCC. Down regulation of β-catenin and plakoglobin was observed in CIN and invasive SCC. N-cadherin was present in normal ovarian surface epithelium while E and P-cadherin were not detected. An aberrant expression of E, P and N-cadherins was detected in different types of epithelial ovarian cancer samples. There was no marked difference in β-catenin expression in normal/ benign and ovarian cancer tissue whereas there was translocation of plakoglobin from membrane to nucleus in epithelial ovarian cancer tissues. Immunoblot analysis of cervical and ovarian cancer cell lines showed differential expression of cadherins and catenins.

Conclussions: Our data demonstrate an aberrant expression of cadherins and catenins in cervical and ovarian cancer. Analysis of their aberrant expression may be useful for the diagnosis of cervical and ovarian cancer at a very early stage and may be used as markers of cancer progression.