Increased expression of hPygo2 is a cellular response to HPV infection in cervical dysplasia

Abstract

We previously demonstrated that the Wnt‐signaling component, hPygo2 was required for cancer growth and that ELF‐1, which is normally regulated by the retinoblastoma (Rb) tumor suppressor, activates hPygo2 expression. Because the E7 protein of Human Papillomavirus (HPV) suppresses Rb function, we hypothesized that hPygo2 expression would be persistent in cervical cells transformed by HPV. Western and immunofluorecence analyses indicated that primary endocervical cell lines (HEN) did not express hPygo2, but that HPV‐transformed endocervical cells and cervical cancer cell lines highly expressed hPygo2. Transfection of a dominant active form of Rb into HPV infected cells reduced hPygo2 expression. Immunohistochemical analysis of hPygo2 and HPV protein expression in a tissue microarray of cervical cancer progression showed weak expression in nuclei of parabasal cells of normal ectocervical epithelium. CIN II and III staged dysplasias showed high levels of expression in cytoplasm and the highest levels of expression were found in squamous cell carcinomas, primarily in the cytoplasm. HPV antibodies stained nuclei and cytoplasm of non‐neoplastic tissues very strongly, and to a lesser extent CINII, III and squamous cell carcinomas. These observations suggested that hPygo2 protein accumulates increasingly with dysplasia leading to frank cancer.