Two prognostic factors in breast cancer: Novel functions of EGFR and beta-catenin

In this study, we demonstrated the novel functions of two important prognostic markers in breast cancer, EGFR and [special characters omitted]-catenin in proliferation and/or other transformation phenotype. First we demonstrated that EGFR could be detected in the nucleus in highly proliferating tissues, including primary breast cancer samples and a breast cancer cell line. We found that EGFR contained a strong transactivation domain, complexed with an AT-rich consensus DNA sequence and activated promoters containing this sequence, including cyclin D1 promoter. Therefore, EGFR may function as a transcription factor to activate genes required for highly proliferating activity such as cyclin D1 in breast cancer. In the second part of this study, we identified [special characters omitted]-catenin as an important prognostic factor in breast cancer. We found that cyclin D1 was one of the genes regulated by [special characters omitted]-catenin in breast cancer cells. The transactivation activity of [special characters omitted]-catenin correlated significantly with cyclin D1 expression in both breast cancer cell lines and in breast cancer patient samples, in which high [special characters omitted]-catenin activity correlated with poor prognosis of the patients. Moreover, blockage of [special characters omitted]-catenin activity significantly inhibited transformation phenotypes in breast cancer cells. Therefore, our results indicate that [special characters omitted]-catenin can be involved in breast cancer formation and/or progression and may serve as a target for breast cancer therapy