EXPRESSION OF TRANSFORMING GROWTH FACTOR-ALPHA AND ITS MESSENGER RIBONUCLEIC-ACID IN HUMAN-BREAST CANCER - ITS REGULATION BY ESTROGEN AND ITS POSSIBLE FUNCTIONAL-SIGNIFICANCE
EXPRESSION OF TRANSFORMING GROWTH FACTOR-ALPHA AND ITS MESSENGER RIBONUCLEIC-ACID IN HUMAN-BREAST CANCER - ITS REGULATION BY ESTROGEN AND ITS POSSIBLE FUNCTIONAL-SIGNIFICANCE
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DOI：
10.1210/mend-2-6-543
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发表时间：
1988-06-01
影响因子：
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通讯作者：
SALOMON, DS
中科院分区：
文献类型：
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作者：
BATES, SE;DAVIDSON, NE;SALOMON, DS
我们已经研究了雌激素调节和转化生长因子α的潜在自分泌作用。（TGF α）在人类乳腺癌细胞系MCF-7中。一种生物活性表观摩尔重量为30 k的TGF α。在MCF-7乳腺癌细胞的条件培养基中通过凝胶过滤色谱法鉴定。我们先前报道了TGF α的诱导。培养基中的水平增加17 β-雌二醇我们现在报道了TGF α的相关增加。通过北方和狭缝印迹分析，在体外雌激素处理后的MCF-7细胞的mRNA。体内实验证实了这些数据：从携带MCF-7肿瘤的裸鼠中撤出雌激素导致肿瘤大小和TGF α下降。mRNA水平。探索TGF α的功能意义。在MCF-7细胞中，抗TGF α。将抗体加入到MCF-7软琼脂克隆测定中。抑制MCF-7生长，支持TGF α的自分泌作用。使用抗EGF受体抗体的进一步实验扩展了该数据，证明了雌激素刺激的单层MCF-7细胞生长的抑制。检查TGF α的一般性。表达，4.8转化酶TGF α。在其他三种人乳腺癌细胞系MDA-MB-231、ZR 75 B和T47 D中观察到mRNA。TGF α的表达用狭缝杂交和北方分析法检测40例雌激素受体阳性和阴性的原发性乳腺肿瘤中70%的mRNA。因此，我们已经证明了TGF α的广泛表达。在人乳腺癌中，其在雌激素应答细胞系中的激素调节，以及其在MCF-7细胞生长中可能的功能意义。
We have studied the estrogenic regulation and the potential autocrine role of transforming growth factor .alpha. (TGF.alpha.) in the human breast cancer cell line MCF-7. A biologically active apparent mol wt 30 k TGF.alpha. was identified by gel filtration chromatography in medium conditioned by MCF-7 breast cancer cells. We previously reported induction of TGF.alpha. levels in medium by 17.beta.-estradiol. We now report correlated increases in TGF.alpha. mRNA, by Northern and slot blot analysis, after estrogen treatment of MCF-7 cells in vitro. In vivo experiments confirmed these data: estrogen withdrawal from MCF-7 tumor-bearing nude mice resulted in a decline in tumor size and TGF.alpha. mRNA levels. To explore the functional significance of TGF.alpha. in MCF-7 cells, anti-TGF.alpha. antibody was added to MCF-7 soft agar cloning assays. Inhibition of MCF-7 growth resulted, supporting an autocrine role for TGF.alpha.. Further experiments using an anti-EGF receptor antibody expanded this data, demonstrating inhibition of estrogen-stimulated monolayer MCF-7 cell growth. Examining the generality of TGF.alpha. expression, 4.8 kilobase TGF.alpha. mRNAs were seen in three other human breast cancer cell lines, MDA-MB-231, ZR 75B, and T47D. Expression of TGF.alpha. mRNA was detected in 70% of estrogen receptor positive and negative primary human breast tumors from 40 patients when examined by slot blot and Northern analysis. Thus, we have demonstrated broad expression of TGF.alpha. in human breast cancer, its hormonal regulation in an estrogen-responsive cell line, and its possible functional significance in MCF-7 cell growth.