Abstract A50: PAR-4 (prostate apoptosis response-4) modulates cell survival and chemosensitivity to docetaxel in MCF-7 breast cancer cells

• Published in: Cancer prevention research (Philadelphia, Pa.) Vol. 5; no. 11_Supplement; p. A50
• Main Authors: Pereira, Michelly C., Bessa-Garcia, Simone A. de, Nagai, Maria A.
• Format: Journal Article
• Language: English
• Published: 01-11-2012
• ISSN: 1940-6207; 1940-6215
• DOI: 10.1158/1940-6207.PREV-12-A50

PAWR (PKC apoptosis WT1 regulator) also known as prostate apoptosis response-4 (PAR-4) was first identified in prostate cancer cells undergoing apoptosis. It encodes a 332-amino-acid protein that induces cancer cell apoptosis, and causes tumor regression by activating Fas/FasL and inhibiting NF-κB activity. Experimental evidence indicates that PAR-4 is a central actor in cancer cell survival and may be a target for cancer-selective targeted therapeutics, however, little is currently known regarding its role in breast cancer tumorigenesis. In this study, we sought to investigate the effects of PAR-4 over-expression and suppression on cell proliferation, apoptosis, and drug sensitivity in breast cancer cells. MCF-7 cells were stably transfected with expression vectors for PAR-4 over-expression, or transiently transfected with siRNA for PAR-4 knockdown. Proliferation assays were performed using MTT, and apoptosis was evaluated using acridine orange staining, fluorescence microscopy, and flow cytometry. PAR-4 over-expression reduced MCF-7 proliferation rates compared with parental or control cells. Conversely, PAR-4 knockdown led to increased MCF-7 proliferation. Par-4 down-regulation also led to increased BCL-2 and reduced BID transcripts. PAR-4 over-expression 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 is mediated by the MAPK/ERK1/2 pathway. MCF-7 cells with increased Par-4 expression showed an increased proportion of early apoptotic cells. Increased Par-4 expression also enhanced the sensitivity of MCF-7 breast cancer cells to docetaxel. PAR-4 has inhibitory effects on breast cancer cell proliferation and survival, and may increase breast cancer cells' chemosensitivity.
Supported by FAPESP and CNPq.
Citation Format: Michelly C. Pereira, Simone A. de Bessa-Garcia, Maria A. Nagai. PAR-4 (prostate apoptosis response-4) modulates cell survival and chemosensitivity to docetaxel in MCF-7 breast cancer cells. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A50.