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

Recent studies from our laboratory have revealed that basic fibroblast grow th factor (bFGF) selectively inhibits the proliferation of human MCF-7 brea st cancer cells. It has also been shown to enhance cis-platinum-induced apo ptosis, decrease levels of the anti-apoptotic gene product bcl-2, and incre ase levels of the cyclin-dependent protein kinase inhibitor p21/WAF1/Cip1. Transforming growth factor beta-1 (TGF beta (1)), a cell growth regulator h as been found to have an inhibitory effect on breast cancer cells. The aim of the present study was to evaluate the possible role of TGF beta (1) in t he antiproliferative effects of bFGF in MCF-7 breast cancer cells. We found that exogenous, as well as endogenous (overexpressed) bFGF increased TGF b eta (1) mRNA expression in the cells and enhanced the secretion of TGF beta (1) into culture medium. However, exogenous addition of TGF beta (1) neith er led to a decrease in bcl-2 nor induced an increase in the levels of p21/ WAF1/Cip1 and neutralizing antibodies to TGF beta (1), did not reverse bFGF -induced G(1) arrest nor the increase in p21/WAF1/Cip1 level. In contrast, antisense oligonucleotides to TGF beta (1) 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 M CF-7 breast cancer cells are mediated by endogenous TGF beta (1), while exo genous TGF beta (1) does not mimic all the effects of bFGF on these breast cancer cells. These findings provide an important basis for further investi gations into the autocrine and paracrine processes that control the growth of breast cancer cells.