Enhancement of ectopic beta-human chorionic gonadotrophin expression by interferon-alpha.
Treatment of three beta-human chorionic gonadotrophin (beta-hCG)-expressing bladder tumour cell lines with interferon-alpha (IFN-alpha) (5000 U/per 10(6) cells) enhanced the rate of beta-hCG secretion from 34.2 +/- 0.9 to 102.5 +/- 0.1 mIU/10(6) cells per 72 h in cell line 5637; 111.15 +/- 11.75 to 261.8 +/- 51.75 mIU/10(6) cells per 72 h in cell line RT112 and 503.25 +/- 28.55 to 1361.65 +/- 110.3 mIU/10(6) cells per 72 h in cell line SCaBER. IFN-gamma had no effect on the rate of beta-hCG secretion. Both interferons reduced the growth rate of the cells: incorporation of radiolabelled thymidine was reduced by 15-45% in the presence of IFN-alpha and by 20-53% with IFN-gamma. Enhancement of beta-hCG secretion by IFN-alpha was dose-dependent over the range 5-50,000 U/10(6) cells. Analysis of cell cycle profiles by flow cytometry showed no increase in the proportion of cells in the G0G1 phase in cultures treated with IFN-alpha. The conceptus of some species produces substances which are either luteotrophic or anti-luteolytic. In sheep, the corpus luteum is maintained by ovine trophoblast protein-I, which has been shown to have structural homology with human IFN-alpha. In primates and a few other higher mammals, early pregnancy is maintained by chorionic gonadotrophin. IFN-alpha is also an early product of the human conceptus. We have now shown that IFN-alpha enhances the ectopic production of the beta-subunit of hCG by bladder tumour cells. This study suggests a direct transcription/translational effect of this cytokine on the expression of a reproductive endocrine gene.
Iles
R K
RK
Department of Reproductive Physiology, St Bartholomew's Hospital Medical College, West Smithfield, London.
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D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D018997:Chorionic Gonadotropin, beta Subunit, Human; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism*; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism
D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D007370:Interferon Type I; D010446:Peptide Fragments