| 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 (TGFβ1), 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 TGFβ1 in the antiproliferative effects of bFGF in MCF-7 breast cancer cells. We found that exogenous, as well as endogenous (overexpressed) bFGF increased TGFβ1 mRNA expression in the cells and enhanced the secretion of TGFβ1 into culture medium. However, exogenous addition of TGFβ1 neither led to a decrease in bcl-2 nor induced an increase in the levels of p21/WAF1/Cip1 and neutralizing antibodies to TGFβ1, did not reverse bFGF-induced G1 arrest nor the increase in p21/WAF1/Cip1 level. In contrast, antisense oligonucleotides to TGFβ1 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 TGFβ1, while exogenous TGFβ1 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. |
| Keywords: |
controlled study; human cell; cisplatin; cell proliferation; gene overexpression; protein bcl 2; apoptosis; breast cancer; gene expression profiling; protein kinase inhibitor; transforming growth factor beta; tumor cells, cultured; breast neoplasms; neovascularization, pathologic; fibroblast growth factor 2; cancer inhibition; blotting, western; messenger rna; reverse transcriptase polymerase chain reaction; rna, messenger; oligonucleotide array sequence analysis; cancer cell; growth regulation; transforming growth factor beta1; autocrine effect; paracrine signaling; protein induction; cyclin-dependent kinase inhibitor p21; cyclins; angiogenesis inhibitors; cell strain mcf 7; protein p21; blotting, northern; growth inhibition; bcl-2; neutralizing antibody; growth inhibitors; basic fibroblast growth factor; antisense oligonucleotide; humans; human; female; priority journal; article; p21/waf1/cip1
|
