Prostate apoptosis response-4 is involved in the apoptosis response to docetaxel in MCF-7 breast cancer cells

Pereira,Michelly   C.; de Bessa-Garcia,Simone  A.; Burikhanov,Ravshan; Pavanelli,Ana  Carolina; Antunes,Lourival; Rangnekar,Vivek  M.; Nagai,Maria   A.

doi:10.3892/ijo.2013.1983

Prostate apoptosis response-4 is involved in the apoptosis response to docetaxel in MCF-7 breast cancer cells

Authors:
- Michelly C. Pereira
- Simone A. de Bessa-Garcia
- Ravshan Burikhanov
- Ana Carolina Pavanelli
- Lourival Antunes
- Vivek M. Rangnekar
- Maria A. Nagai
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Affiliations: Discipline of Oncology, Department of Radiology and Oncology, Faculty of Medicine, University of São Paulo, CEP 01246-903, São Paulo, Brazil, Markey Cancer Center, University of Kentucky, Lexington, KY, USA
Published online on: June 12, 2013 https://doi.org/10.3892/ijo.2013.1983
Pages: 531-538

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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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