COX inhibitors modulate bFGF-induced cell survival in MCF-7 breast cancer cells.

Autor: Teh SH; Department of Surgery, St. Vincent's University Hospital and The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland., Hill AK, Foley DA, McDermott EW, O'Higgins NJ, Young LS
Jazyk: angličtina
Zdroj: Journal of cellular biochemistry [J Cell Biochem] 2004 Mar 01; Vol. 91 (4), pp. 796-807.
DOI: 10.1002/jcb.10767
Abstrakt: Basic fibroblast growth factor (bFGF) serves as a modulator of survival in breast cancer cells. The mechanisms by which bFGF transduces the anti-apoptotic signal and interacts with COX inhibitors were investigated. bFGF reduced apoptosis in MCF-7 breast cancer cells and up-regulated the expression of mitocondrial Bcl-2, whereas COX inhibitors meloxicam (selective COX-2) and aspirin (non-selective), induced apoptosis. bFGF up-regulated survivin protein expression and induced cdc-2 phosphorylation moderately at early (2-6 h), and substantially at late (24 h), time-points. Survivin mRNA expression was up-regulated only at the later time-point. COX inhibitors prevented up-regulation of survivin protein expression at both 2 and 24 h and prevented early modest increases in cdc-2 phosphorylation. Up-regulation of survivin mRNA was not found to be modulated by the COX-2 inhibitor meloxicam. bFGF regulation of survivin expression was found to be ERK1/2 kinase dependent and bFGF-induced phosphorylation of c-raf was prevented by the COX-2 inhibitor. bFGF was, however, unable to induce COX-2 protein expression or modulate COX-2 activity in MCF-7 cells as evidenced by unaltered PGE(2) production. These results indicate that bFGF regulates survivin expression in MCF-7 breast cancer cells by signaling through an ERK1/2 dependent pathway. COX-2 inhibitors can modulate bFGF-induced survivin expression in a COX-2 independent manner.
(Copyright 2004 Wiley-Liss, Inc.)
Databáze: MEDLINE
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