Activator Protein-2β Promotes Tumor Growth and Predicts Poor Prognosis in Breast Cancer

Abstract

Background/Aims: Activator protein-2 (AP-2) transcription factors have been proved to be essential in maintaining cellular homeostasis and regulating the transformation from normal growth to neoplasia. However, the role of AP-2β, a key member of AP-2 family, in breast cancer is rarely reported. Methods: The effect of AP-2 on cell growth, migration and invasion in breast cancer cells were measured by MTT, colony formation, wound-healing and transwell assays, respectively. The expression levels of AP-2β and other specific markers in breast cancer cell lines and tissue microarrays from the patients were detected using RT-PCR, Western blot and immunohistochemical staining. The regulation of AP-2β on tumor growth in vivo was analyzed in a mouse xenograft model. Results: We demonstrated the tumor-promoting function of AP-2β in breast cancer. AP-2β was found to be highly expressed in breast cancer cell lines and tumor tissues of breast cancer patients. The shRNA-mediated silencing of AP-2β led to the dramatic inhibition of cell proliferation, colony formation ability, migration and invasiveness in breast cancer cells accompanied by the down-regulated expression of some key proteins involved in cancer progression, including p75, MMP-2, MMP-9, C-Jun, p-ERK and STAT3. Overexpression of AP-2β markedly up-regulated the levels of these proteins. Consistent with the in vitro study, the silencing or overexpression of AP-2β blocked or promoted tumor growth in the mice with xenografts of breast cancers. Notably, the high AP-2β expression levels was correlated with poor prognosis and advanced malignancy in patients with breast cancer. Conclusions: Our study demonstrates that AP-2β promotes tumor growth and predicts poor prognosis, and may represent a potential therapeutic target for breast cancer.

Keywords

• Ap-2β
• Breast cancer
• Prognosis