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Progestins Increase Insulin Receptor Content and Insulin Stimulation of Growth in Human Breast Carcinoma Cells¹

Division of Diabetes and Endocrine Research, Mount Zion Medical Center of the University of California, San Francisco, California 94120 [V. P., A. B., I. D. G.]; Department of Obstetrics, Gynecology and Reproductive Sciences [C. C. R., P. K. S.], and Departments of Medicine and Physiology [I. D. G.], University of California, San Francisco, California 94143; and Cattedra di Endocrinologia dell'Universita'di Catania, Ospedale Garibaldi, 95123 Cantania, Italy [R. V.]

The effects of progesterone on the growth of breast carcinoma cells are undefined. In the present study we investigated the effect of progestins on insulin receptor gene expression and insulin action in human breast cancer cells. Treatment of T47D cells with the synthetic progestin R5020 induced a time- and dose-dependent increase in insulin receptor content as measured by both ligand-binding studies and radioimmunoassay. Binding was half-maximally stimulated at 300 pM R5020 and maximal levels were reached after 4 days of treatment. Progesterone was 10-fold less potent than R5020. Cortisol had no effect on insulin receptor levels, while 17ß-estradiol and dihydrotestosterone had minimal effects. Progestin treatment both increased insulin receptor mRNA levels and altered the relative distribution of the multiple insulin receptor mRNA transcripts. In order to study the functional significance of the increased insulin receptor levels, we incubated T47D cells with progesterone and then treated them with insulin. Insulin alone had a small effect on cell growth; however, the effect of insulin was markedly potentiated by progesterone treatment. These studies in breast cancer cells demonstrate, therefore, that insulin receptor gene expression is under the regulation of progestins and raise the possibility that progestin-insulin interactions may regulate breast cancer cell growth in vivo.

¹ This work was supported by the John A. Kerner Foundation; USPHS Grant (CA 39825 A) awarded by the National Cancer Institute, DHHS; and Associzione Italiana Ricerca sul Cancro.

² To whom reprint request should be addressed, at Division of Diabetes and Endocrine Research, Mount Zion Medical Center, P.O. Box 7921, San Francisco, CA 94120-7921.

Received 5/ 1/90. Accepted 9/13/90.

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