Send to

Choose Destination
See comment in PubMed Commons below
Neoplasia. 2006 Jul;8(7):568-77.

AP-2gamma induces p21 expression, arrests cell cycle, and inhibits the tumor growth of human carcinoma cells.

Author information

Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA.


Activating enhancer-binding protein 2gamma (AP-2gamma) is a member of the developmentally regulated AP-2 transcription factor family that regulates the expression of many downstream genes. Whereas the effects of AP-2alpha overexpression on cell growth are fairly well established, the cellular effects of AP-2gamma overexpression are less well studied. Our new findings show that AP-2gamma significantly upregulates p21 mRNA and proteins, inhibits cell growth, and decreases clonogenic survival. Cell cycle analysis revealed that forced AP-2gamma expression induced G1-phase arrest, decreased DNA synthesis, and decreased the fraction of cells in S phase. AP-2gamma expression also led to cyclin D1 repression, decreased Rb phosphorylation, and decreased E2F activity in breast carcinoma cells. AP-2gamma binding to the p21 promoter was observed in vivo, and the absence of growth inhibition in response to AP-2gamma expression in p21(-/-) cells demonstrated that p21 caused, at least in part, AP-2-induced cell cycle arrest. Finally, the tumor growth of human breast carcinoma cells in vivo was inhibited by the expression of AP-2gamma relative to empty vector-infected cells, suggesting that AP-2gamma acts as a tumor suppressor. In summary, expression of either AP-2gamma or AP-2alpha inhibited breast carcinoma cell growth; thus, these genes may be therapeutic targets for breast cancer.

[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for PubMed Central
    Loading ...
    Support Center