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Title: Prostate apoptosis response-4 is involved in the apoptosis response to docetaxel in MCF-7 breast cancer cells
Authors: PEREIRA, Michelly C.BESSA-GARCIA, Simone A. DeBURIKHANOV, RavshanPAVANELLI, Ana CarolinaANTUNES, LourivalRANGNEKAR, Vivek M.NAGAI, Maria A.
Citation: INTERNATIONAL JOURNAL OF ONCOLOGY, v.43, n.2, p.531-538, 2013
Abstract: 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.
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Artigos e Materiais de Revistas Científicas - FM/MDR
Departamento de Radiologia - FM/MDR

Artigos e Materiais de Revistas Científicas - LIM/24
LIM/24 - Laboratório de Oncologia Experimental

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