Advanced search
Start date
Betweenand
(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

Full text
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 Opportunities: Regular Research Grants