Pereira, Michelly C.
De Bessa-Garcia, Simone A.
Pavanelli, Ana Carolina
Rangnekar, Vivek M.
Nagai, Maria A.
Total Authors: 7
 Univ Sao Paulo, Discipline Oncol, Dept Radiol & Oncol, Fac Med, BR-01246903 Sao Paulo - Brazil
 Univ Sao Paulo, Lab Genet Mol, Ctr Translat Res Oncol, BR-01246000 Sao Paulo - Brazil
 Univ Kentucky, Lucille P Markey Canc Ctr, Lexington, KY - USA
Total Affiliations: 3
International Journal of Oncology;
Web of Science Citations:
Experimental evidence indicates that prostate apoptosis response-4 (Par-4, also known as PAWR) is a key regulator of cancer cell survival and may be a target for cancer-selective targeted therapeutics. Par-4 was first identified in prostate cancer cells undergoing apoptosis. Both intracellular and extracellular Par-4 have been implicated in apoptosis. Relatively little is known about the role of Par-4 in breast cancer cell apoptosis. In this study, we sought to investigate the effects of Par-4 expression on cell proliferation, apoptosis and drug sensitivity in breast cancer cells. MCF-7 cells were stably transfected with expression vectors for Par-4, or transiently transfected with siRNA for Par-4 knockdown. Cell proliferation assays were performed using MTT and apoptosis was evaluated using acridine orange staining, fluorescence microscopy and flow cytometry. Par-4 overexpression reduced MCF-7 proliferation rates. Conversely, Par-4 knockdown led to increased MCF-7 proliferation. Par-4 downregulation also led to increased BCL-2 and reduced BID expression. Par-4 overexpression did not affect the cell cycle profile. However, MCF-7 cells with increased Par-4 expression showed reduced ERK phosphorylation, suggesting that the inhibition of cell proliferation promoted by Par-4 may be mediated by the MAPK/ERK1/2 pathway. MCF-7 cells with increased Par-4 expression showed a marginal increase in early apoptotic cells. Importantly, we found that Par-4 expression modulates apoptosis in response to docetaxel in MCF7 breast cancer cells. Par-4 exerts growth inhibitory effects on breast cancer cells and chemosensitizes them to docetaxel. (AU)