Expression of Transforming Growth Factor α and its Messenger Ribonucleic Acid in Human Breast Cancer: Its Regulation by Estrogen and its Possible Functional Significance

We have studied the estrogenic regulation and the potential autocrine role of transforming growth factor α (TGFα) in the human breast cancer cell line MCF-7. A biologically active apparent mol wt 30 k TGFα was identified by gel filtration chromatography in medium conditioned by MCF-7 breast cancer cells. We previously reported induction of TGFα levels in medium by 17β-estradiol. We now report correlated increases in TGFα 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 TGFα mRNA levels. To explore the functional significance of TGFα in MCF-7 cells, anti-TGFα antibody was added to MCF-7 soft agar cloning assays. Inhibition of MCF-7 growth resulted, supporting an autocrine role for TGFα. 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 TGFα expression, 4.8 kilobase TGFα mRNAs were seen in three other human breast cancer cell lines, MDA-MB-231, ZR 75B, and T47D. Expression of TGFα 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 TGFα in human breast cancer, its hormonal regulation in an estrogen-responsive cell line, and its possible functional significance in MCF-7 cell growth.