Work

AP-2γ Induces p21 Expression, Arrests Cell Cycle, Inhibits the Tumor Growth of Human Carcinoma Cells

Year: 2006

Type: article

Abstract: 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.

Source: Neoplasia

DOI: 10.1593/neo.06367

Authors: Hualei Li, Prabhat C. Goswami, Frederick E. Domann

Institution: University of Iowa

Language: English

Topic: Cancer-related Molecular Pathways

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,530