AP-2α Interacts With Pokemon In Regulating Survivin Expression In MCF-7 Cells

Transcription factor Pokemon, known as a proto-oncogene, participates in embryonic development and differentiation and has also been recently implicated in carcinogenesis. Survivin is a new member of the inhibitor of apoptosis protein family and its aberrant expression is implicated with tumorigenesis, cancer progression, drug resistance and shorter patient survival, and the regulation of the survivin expression is of importance in cancer prevention and treatment. In the present work, we showed that survivin promoter activity is negatively regulated by AP-2a through its direct binding to the core sequence of the promoter in MCF-7 cells. Furthermore, it was found that pokemon abrogated the negative effect of AP-2a on the survivin expression via binding to AP-2a protein with its POZ domain in MCF-7 cells. Moreover, the over expression of AP-2a sensitized breast cancer cells to doxorubicin treatment, and the knockdown of AP-2a leaded to a increased resistance of MCF-7 cells to doxorubicin. Those findings provide new insights into the regulatory network for survivin gene expression, and will be usable in cancer prevention and treatment.