Role of transforming growth factor beta in the growth inhibition of human breast cancer cells by basic fibroblast growth factor
Role of transforming growth factor beta in the growth inhibition of human breast cancer cells by basic fibroblast growth factor
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DOI：
10.1023/a:1012522321762
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发表时间：
2001-01-01
影响因子：
3.8
通讯作者：
Nordenberg, J
中科院分区：
文献类型：
--
作者：
Fenig, E;Kanfi, Y;Nordenberg, J
本实验室最近的研究表明，碱性成纤维细胞生长因子(BFGF)选择性地抑制人乳腺癌细胞MCF-7的增殖。它还被证明能增强顺铂诱导的细胞凋亡，降低抗凋亡基因产物bcl-2的水平，并增加细胞周期蛋白依赖的蛋白激酶抑制物p21/WAF1/Cip1的水平。转化生长因子β1(TGFβ1)是一种细胞生长调节剂，对乳腺癌细胞有抑制作用。本研究的目的是评价转化生长因子β(1)在碱性成纤维细胞生长因子抑制MCF-7乳腺癌细胞增殖中的作用。我们发现，外源性以及内源性(过表达)的bFGF增加了细胞内转化生长因子β(1)的mRNA表达，并促进了培养上清液中转化生长因子β(1)的分泌。然而，外源性加入转化生长因子β(1)既不能降低bc1-2的表达，也不能增加p21/WAF1/Cip1和抗转化生长因子β(1)中和抗体的水平，也不能逆转bFGF诱导的G(1)期阻滞和p21/WAF1/Cip1水平的升高。相反，转化生长因子β(1)的反义寡核苷酸(1)可抑制bFGF对MCF-7细胞p21/WAF1/Cip1的诱导增殖作用。这些数据表明，bFGF对人MCF-7乳腺癌细胞的抗增殖作用是由内源性转化生长因子β(1)介导的，而外源性转化生长因子β(1)并不能模仿bFGF对这些乳腺癌细胞的全部作用。这些发现为进一步研究控制乳腺癌细胞生长的自分泌和旁分泌过程提供了重要基础。
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 (TGF beta (1)), 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 TGF beta (1) in the antiproliferative effects of bFGF in MCF-7 breast cancer cells. We found that exogenous, as well as endogenous (overexpressed) bFGF increased TGF beta (1) mRNA expression in the cells and enhanced the secretion of TGF beta (1) into culture medium. However, exogenous addition of TGF beta (1) neither 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 MCF-7 breast cancer cells are mediated by endogenous TGF beta (1), while exogenous TGF beta (1) 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.