Back to Search
Start Over
Genistein induces enhanced growth promotion in ER-positive/erbB-2-overexpressing breast cancers by ER–erbB-2 cross talk and p27/kip1 downregulation.
- Source :
-
Carcinogenesis . Apr2010, Vol. 31 Issue 4, p695-702. 8p. 6 Graphs. - Publication Year :
- 2010
-
Abstract
- Genistein is a major isoflavone with known hormonal and tyrosine kinase-modulating activities. Genistein has been shown to promote the growth of estrogen receptor positive (ER+) MCF-7 cells. In ER-negative (ER−)/erbB-2-overexpressing (erbB-2+) cells, genistein has been shown to inhibit cell growth through its tyrosine kinase inhibitor activity. The effects of genistein on cell growth and tamoxifen response in ER+/erbB-2-altered breast cancers (known as luminal type B and noted in ∼10 to 20% of breast cancers) have not been well explored. Using erbB-2-transfected ER+ MCF-7 cells, we found that genistein induced enhanced cellular proliferation and tamoxifen resistance when compared with control MCF-7 cells. These responses were accompanied by increased phosphorylation of ERα and ER signaling, without increase in ER protein levels. Genistein-treated MCF-7/erbB-2 cells also showed enhanced activation/phosphorylation of erbB-2, Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase. Blockade of the phosphatidylinositol 3-kinase and/or MAPK pathways abrogated genistein-induced growth promotion, suggesting that genistein effects involve both critical signaling pathways. We also found that p27/kip1 was markedly downregulated in genistein-treated MCF-7/erbB-2 cells. Overexpression of p27/kip1 attenuated genistein-mediated growth promotion. In aggregate, our data suggest that the concomitant coexpression of ER and erbB-2 makes breast cancers particularly susceptible to the growth-promoting effects of genistein across a wide range of doses. The underlying mechanisms involve enhanced ER–erbB-2 cross talk and p27/kip1 downregulation. [ABSTRACT FROM PUBLISHER]
- Subjects :
- *GENISTEIN
*BREAST cancer
*ESTROGEN receptors
*CELL proliferation
*ISOFLAVONES
Subjects
Details
- Language :
- English
- ISSN :
- 01433334
- Volume :
- 31
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 51494068
- Full Text :
- https://doi.org/10.1093/carcin/bgq007