Progesterone receptor (PR) inhibits expression of insulin-like growth factor-binding protein-1 (IGFBP-1) in human endometrial cell line HEC-1B: characterization of the inhibitory effect of PR on the distal promoter region of the IGFBP-1 gene

Molecular Endocrinology
J Gao, L Tseng

Abstract

Progestin has been shown to have both stimulatory and inhibitory effects on the expression of insulin-like growth factor binding protein-1 (IGFBP-1) in human endometrial cells. In this study, progestin was found to reduce levels of secreted IGFBP-1 and IGFBP-1 messenger RNA and IGFBP-1 promoter activity after stably transfecting a progesterone receptor (PR; B form) expression vector into HEC-1B cells. Deletion analysis of the IGFBP-1 promoter revealed that PR specifically inhibited promoter activity derived from a 59-bp distal BsaHI/RsaI fragment. It was concluded that PR inhibited the promoter activity through protein-protein interactions based on the facts that 1) no progesterone-responsive element was revealed by a series block mutation in the BsaHI/RsaI fragment; 2) PR bound by the antiprogesterone ZK98299 inhibited IGFBP-1 promoter activity; 3) a DNA-binding mutant of PR inhibited the IGFBP-1 promoter activity; and 4) in an in vivo competition assay, the DNA-binding domain of PR did not release the inhibitory effect of intact PR. Analysis of PR deletion mutants indicated that both transcriptional activation domains of PR (TAF-1 and TAF-2) were involved in the inhibition of IGFBP-1 expression. Thus, our data may explain the...Continue Reading

References

Sep 1, 1992·International Journal of Gynaecology and Obstetrics : the Official Organ of the International Federation of Gynaecology and Obstetrics·E M Rutanen, M Seppälä
Jan 1, 1991·Annual Review of Genetics·H Gronemeyer
Aug 1, 1987·Molecular and Cellular Biology·C Chen, H Okayama
Feb 1, 1987·Molecular and Cellular Biology·J R de WetS Subramani
Oct 1, 1993·Proceedings of the Society for Experimental Biology and Medicine·P D LeeD R Powell
Aug 1, 1993·Molecular Reproduction and Development·D R Clemmons
Sep 1, 1993·Molecular and Cellular Endocrinology·G D Bryant-GreenwoodS Y Yamamoto

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Citations

Oct 26, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M A CrisseyR Taub
Sep 14, 2002·Human Cell·Hiroyuki KurarmotoManami Imai
Jul 22, 2020·Molecular Reproduction and Development·William NelsonYu-Bin Ding

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