Enhancement of ectopic β-human chorionic gonadotrophin expression by interferon-α
ABSTRACT Treatment of three β-human chorionic gonadotrophin (β-hCG)-expressing bladder tumour cell lines with interferon-α (IFN-α) (5000 U/per 106 cells) enhanced the rate of β-hCG secretion from 34·2 ±0·9 to 102·5 ± 0·1 mIU/106 cells per 72 h in cell line 5637; 111·15 ± 11·75 to 261·8± 51·75 mIU/106 cells per 72 h in cell line RT112 and 503·25 ± 28·55 to 1361·65± 110·3 mIU/106 cells per 72 h in cell line SCaBER. IFN-γ had no effect on the rate of β-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-α and by 20–53% with IFN-γ. Enhancement of β-hCG secretion by IFN-α was dose-dependent over the range 5–50 000 U/106 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-α. 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-α. In primates and a few other higher mammals, early pregnancy is maintained by chorionic gonadotrophin. IFN-α is also an early product of the human conceptus. We have now shown that IFN-α enhances the ectopic production of the β-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. Journal of Endocrinology (1989) 123, 501–507