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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Pereira, Michelly C. [1, 2] ; De Bessa-Garcia, Simone A. [1, 2] ; Burikhanov, Ravshan [3] ; Pavanelli, Ana Carolina [1, 2] ; Antunes, Lourival [1, 2] ; Rangnekar, Vivek M. [3] ; Nagai, Maria A. [1, 2]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Discipline Oncol, Dept Radiol & Oncol, Fac Med, BR-01246903 Sao Paulo - Brazil
[2] Univ Sao Paulo, Lab Genet Mol, Ctr Translat Res Oncol, BR-01246000 Sao Paulo - Brazil
[3] Univ Kentucky, Lucille P Markey Canc Ctr, Lexington, KY - USA
Total Affiliations: 3
Document type: Journal article
Source: International Journal of Oncology; v. 43, n. 2, p. 531-538, AUG 2013.
Web of Science Citations: 11
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. (AU)

FAPESP's process: 10/16543-5 - Study of the functional role of PAR-4 and SPARC in breast cancer cell survival and chemosensitivity
Grantee:Maria Aparecida Nagai
Support type: Regular Research Grants