Fatty acid synthetase and its mRNA are induced by progestins in breast cancer cells.

The growth of hormone-dependent breast cancer cell lines (MCF7 and T47D) is inhibited in vitro by progestins which also induce several proteins. We have cloned cDNA sequences corresponding to one of them, a 250-kDa protein, and have shown that the corresponding mRNA is also rapidly induced by progestins (Chalbos D., Westley B., May F.E.B., Alibert C., and Rochefort H. (1986) Nucleic Acids Res. 14, 965-982). We show here that the 250-kDa protein is very similar, if not identical, to fatty acid synthetase: fatty acid synthetase is regulated to the same extent by progestins, the 250-kDa protein is specifically immunoprecipitated by antibodies to fatty acid synthetase, and fatty acid synthetase covalently labeled by [14C]pantothenate is immunoprecipitated by antibodies to the 250-kDa protein. The induction of fatty acid synthetase by progestin in cancer cells thus provides another model for studying the mechanism regulating steroid transcription in human cells. Since fatty acid synthetase regulation by progestins appears to be the opposite in cancer and normal mammary cells, this observation may also be a clue for understanding the role of progestins in mammary carcinogenesis.