Effect of alpha-interferon, 17 beta-estradiol, and tamoxifen on estrogen receptor concentration and cell cycle kinetics of MCF 7 cells.
The interaction of alpha-interferon, 17 beta-estradiol, and tamoxifen on estrogen receptor content, growth fraction, proliferative rate, and total protein synthesis of MCF 7 cells was investigated under culture conditions (minus phenol red and at low concentrations of "stripped" fetal calf serum) allowing for direct stimulation of proliferation by estrogens. Exposure to estradiol alone resulted in a decrease of estrogen receptor content as measured by immunoassay, an increase of the proportion of cells in S phase, and increases in cell proliferation as well as total protein synthesis. alpha-Interferon treatment resulted in cell cycle arrest with reduced proliferation, an increase of estrogen receptor content, but a decrease in the rate of total protein synthesis. Pretreatment with alpha-interferon inhibited the estrogen induced stimulation of cell growth as well as the associated decrease of estrogen receptor content. Tamoxifen treatment resulted in decreased cell proliferation and decrease of estrogen receptor content and of total protein synthesis. These results suggest that the estrogen receptor concentration of MCF 7 cells is growth fraction related. Pretreatment with alpha-interferon enhanced the inhibitory effect of tamoxifen on cell proliferation while preventing the tamoxifen induced reduction of estrogen receptor content. The synergistic effect of alpha-interferon and tamoxifen are most marked following 72 h pretreatment with interferon, when the maximum interferon induced increase of estrogen receptor concentration is evident. The mechanism is thus due probably to an increase of cellular receptor as a ligand for tamoxifen binding and suggests a possible role for the clinical use of interferons combined with tamoxifen.
Bezwoda
W R
WR
Department of Medicine, University of Witwatersrand, Johannesburg, South Africa.
Meyer
K
K
D001943:Breast Neoplasms; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007700:Kinetics; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D007370:Interferon Type I; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D013629:Tamoxifen; D004958:Estradiol