Parole chiave: Estradiol, Hydrocortisone, Insulin, Insulin Receptor, Messenger Rna, Progesterone, Promegestone, Testosterone, Article, Breast Carcinoma, Female, Growth Stimulation, Human, Human Cell, Priority Journal, Antibodies, Monoclonal, Breast Neoplasms, Cell Division, Cell Line, Drug Synergism, Immunoglobulin G, Insulin-Like Growth Factor I, Kinetics, Support, Non-U.S. Gov, P.H.S., Transcription, Genetic, Non-U. S. Gov, P. H. S.,
Division of Diabetes and Endocrine Research, Mount Zion Medical Center, University of California, P.O. Box 7921, San Francisco, CA 94120, United States
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 17β-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.
41 Records (36 escludendo Abstract e Conferenze). Impact factor totale: 204.702 (186.752 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 196.211 (184.663 escludendo Abstract e Conferenze).