Arrick B A, Korc M, Derynck R
Department of Developmental Biology, Genentech, Inc., South San Francisco, California 94080.
Cancer Res. 1990 Jan 15;50(2):299-303.
Transforming growth factor (TGF)-beta is a potent regulator of many cell functions and a growth inhibitor for mammary epithelial cells. We now know of three highly homologous members of the human TGF-beta gene family. We have studied the expression of TGF-beta 1, -beta 2, and -beta 3 mRNA in four human breast cancer cell lines. Using the RNase protection assay, we have detected mRNA expression of TGF-beta 1, -beta 2, and -beta 3 by T-47D cells, TGF-beta 1 and -beta 3 by ZR-75-1 cells, and TGF-beta 1 by MCF-7 cells. Treatment of these estrogen receptor-positive cells with 10 nM estradiol for 48 h resulted in decreased mRNA levels of TGF-beta 2 and -beta 3 but did not affect mRNA levels of TGF-beta 1. Expression of TGF-beta 1 and -beta 2 mRNA by an estrogen receptor-negative cell line, MDA-MB-231, was not changed by estradiol treatment. Treatment of cells with the antiestrogen tamoxifen (1 microM) did not significantly alter mRNA levels for any of the three TGF-beta species. We have further determined that estradiol treatment of T-47D was associated with diminished secretion of TGF-beta into the medium. Both TGF-beta 1 and -beta 2 inhibited the proliferation of MCF-7 cells, and neither protein affected the growth of T-47D cells. TGF-beta 1 was at least 10-fold more potent than TGF-beta 2 at inhibiting the growth of MCF-7 cells.
转化生长因子（TGF）-β是多种细胞功能的强效调节剂，也是乳腺上皮细胞的生长抑制剂。我们现在已知人类TGF-β基因家族有三个高度同源的成员。我们研究了四种人乳腺癌细胞系中TGF-β1、-β2和-β3 mRNA的表达。使用核糖核酸酶保护分析，我们检测到T-47D细胞表达TGF-β1、-β2和-β3的mRNA，ZR-75-1细胞表达TGF-β1和-β3的mRNA，MCF-7细胞表达TGF-β1的mRNA。用10 nM雌二醇处理这些雌激素受体阳性细胞48小时，导致TGF-β2和-β3的mRNA水平降低，但不影响TGF-β1的mRNA水平。雌激素受体阴性细胞系MDA-MB-231表达的TGF-β1和-β2 mRNA不受雌二醇处理的影响。用抗雌激素他莫昔芬（1 microM）处理细胞，对三种TGF-β亚型的mRNA水平均无显著影响。我们进一步确定，用雌二醇处理T-47D细胞与培养基中TGF-β分泌减少有关。TGF-β1和-β2均抑制MCF-7细胞的增殖，两种蛋白均不影响T-47D细胞的生长。在抑制MCF-7细胞生长方面，TGF-β1的效力至少比TGF-β2高10倍。
