Progesterone sensitizes breast cancer MCF7 cells to imatinib inhibitory effects

• Type: Article in International Scientific Journal
• Date: 2008

Authors

rocha, a (Author) Other; azevedo, i (Author) Other; soares, r (Author) FMUP

Journal

Title: Journal of Cellular Biochemistry

Vol. 103 No. 607

Pages: 607-614

ISSN: 0730-2312

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 9 Citations

Scientific classification

CORDIS: Health sciences

Other information

Authenticus ID: P-004-1T2

DOI: 10.1002/jcb.21432

Abstract (EN): In previous Studies, we found that progesterone was able to induce the expression of platelet-derived growth factor (PDGF) in human breast cancer MCF7 cells. Knowing that imatinib rnesylate targets PDGF receptor tyrosine kinase activity, the aim of the present study was to examine the effects of imatinib on progesterone-treated MCF7 cells. Expression of phosphorylated (activated) platelet-derived growth factor receptor-alpha (PDGFR alpha) was detected in MCF7 cells. Interestingly, phosphorylated-PDGFR alpha expression was significantly downregulated by imatinib. The effects of imatinib oil cell growth, apoptosis and migration were then analyzed. Imatinib effectively inhibited anchorage-dependent colony formation, and cell viability as evaluated by MTT assay. Corroborating these findings, a significant increase in the percentage of apoptotic cells was also observed when cells were treated with imatinib. Surprisingly, these inhibitory effects were all enhanced by the presence of progesterone. Cell migration assays did also show a reduction in the migratory capacity after incubation with imatinib. These findings reveal that imatimb acts by decreasing MCF7 cell viability, growth and migration, with concomitant increase in apoptosis. Furthermore, incubation with progesterone seems to prompt cells to the inhibitory action of imatimb, probably by sustaining PDGFRa activity. The Current Study Points Out imatinib as a possible therapeutic strategy in progesterone-dependent breast cancer.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8