Role of transforming growth factor beta in the growth inhibition of human breast cancer cells by basic fibroblast growth factor.

Abstract

Recent studies from our laboratory have revealed that basic fibroblast growth factor (bFGF) selectively inhibits the proliferation of human MCF-7 breast cancer cells. It has also been shown to enhance cis-platinum-induced apoptosis, decrease levels of the anti-apoptotic gene product bcl-2, and increase levels of the cyclin-dependent protein kinase inhibitor p21/WAF1/Cip1. Transforming growth factor beta-1 (TGFbeta1), a cell growth regulator has been found to have an inhibitory effect on breast cancer cells. The aim of the present study was to evaluate the possible role of TGFbeta1 in the antiproliferative effects of bFGF in MCF-7 breast cancer cells. We found that exogenous, as well as endogenous (overexpressed) bFGF increased TGFbeta1 mRNA expression in the cells and enhanced the secretion of TGFbeta1 into culture medium. However, exogenous addition of TGFbeta1 neither led to a decrease in bcl-2 nor induced an increase in the levels of p21/WAF1/Cip1 and neutralizing antibodies to TGFbeta1, did not reverse bFGF-induced G1 arrest northe increase in p21/WAF1/Cip1 level. In contrast, antisense oligonucleotides to TGFbeta1 abrogated the antiproliferative effects and inhibited the induction of p21/WAF1/Cip1 by bFGF in MCF-7 cells. These data suggest that the anti-proliferative effects of bFGF in human MCF-7 breast cancer cells are mediated by endogenous TGFbeta1, while exogenous TGFbeta1 does not mimic all the effects of bFGF on these breast cancer cells. These findings provide an important basis for further investigations into the autocrine and paracrine processes that control the growth of breast cancer cells.

• Authors: E Fenig, Y Kanfi, Q Wang, E Beery, T Livnat, L Wasserman, G Lilling, J Yahalom, R Wieder, J Nordenberg
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 70 Issue 1 Pg. 27-37 (Nov 2001) ISSN: 0167-6806 [Print] Netherlands
• PMID: 11767002 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Angiogenesis Inhibitors
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins
• Growth Inhibitors
• RNA, Messenger
• TGFB1 protein, human
• Transforming Growth Factor beta
• Transforming Growth Factor beta1
• Fibroblast Growth Factor 2

Topics

• Angiogenesis Inhibitors (metabolism, pharmacology)
• Blotting, Northern
• Blotting, Western
• Breast Neoplasms (blood supply, drug therapy, metabolism)
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins (genetics, metabolism)
• Female
• Fibroblast Growth Factor 2 (genetics, metabolism, pharmacology)
• Gene Expression Profiling
• Growth Inhibitors (genetics, metabolism)
• Humans
• Neovascularization, Pathologic (metabolism, prevention & control)
• Oligonucleotide Array Sequence Analysis
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Transforming Growth Factor beta (genetics, metabolism, pharmacology)
• Transforming Growth Factor beta1
• Tumor Cells, Cultured