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.

WWOX Loses the Ability to Regulate Oncogenic AP-2γ and Synergizes with Tumor Suppressor AP-2α in High-Grade Bladder Cancer

“…Such observations are different from previous research, where AP-2γ was localized in the nucleus regardless of the expression status and was only altered due to sequestration by WWOX [15]. Although no literature data concern AP-2γ, Li et al found oncogenic AP-2β to be synchronously localized in both nucleus and cytoplasm in breast cancer patients with high AP-2β expression; no cytoplasmic distribution was observed in patients with low AP-2β [43]. Considering the similar nature of AP-2γ, this relocation might be attributed to overexpression, serving as a purposeful mechanism of tumor development.…”

“…Such AP-2γ nature might be related to c-MYC inhibition (to suppress apoptosis) or an increase of EGFR (to intensify proliferation) [45,46]. However, the impact on the mitochondrial redox potential needs reference to AP-2β, whose knockdown suppressed the cell viability in breast cancer [43]. Interestingly, WWOX overexpression in W/C did not alter AP-2γ function, but its separate overexpression (W/K) shows an anti-cancer effect via the induction of apoptosis or inhibition of cell viability and proliferation.…”

DHX33 Interacts with AP-2β To Regulate Bcl-2 Gene Expression and Promote Cancer Cell Survival

“…Standard protocol was then followed using a Dako kit according to the manufacturer's recommendations. The staining intensity was then scored as follows based on criteria described previously (35): 0, no staining; 1, weak; 2, moderate; and 3, strong. The percentages of positively stained cells were rated 1, 2, or 3 if the values were Ͻ25%, 25 to 50%, or Ͼ50%, respectively.…”

NPNT promotes early-stage bone metastases in breast cancer by regulation of the osteogenic niche

“…Transwell assay was performed as previously reported [17]. The lower chambers of 24-well chemotaxis chambers (Corning, CA, USA) were filled with 600 µl medium containing 10% fetal bovine serum.…”