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

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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.

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Authors and Affiliations

  1. Felsenstein Medical Research Institute, Endocrinology Laboratory, Oncology Institute, Rabin Medical Center, Petah Tiqva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Eyal Fenig, Yariv Kanfi, Einat Beery, Tamar Livnat, Lina Wasserman, Gila Lilling & Jardena Nordenberg

  2. Department of Medicine, Division of Oncology, UMDNJ-New Jersey Medical School, Newark, NJ

    Qin Wang & Robert Wieder

  3. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY

    Joachim Yahalom

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  1. Eyal Fenig
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  2. Yariv Kanfi
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  3. Qin Wang
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  4. Einat Beery
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  5. Tamar Livnat
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  9. Robert Wieder
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  10. Jardena Nordenberg
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Fenig, E., Kanfi, Y., Wang, Q. et al. Role of transforming growth factor beta in the growth inhibition of human breast cancer cells by basic fibroblast growth factor. Breast Cancer Res Treat 70, 27–37 (2001). https://doi.org/10.1023/A:1012522321762

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