Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 277, Issue 31, Pages 27793-27800Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M202584200
Keywords
-
Categories
Funding
- NCI NIH HHS [CA26869, CA90073 F32] Funding Source: Medline
- NIDDK NIH HHS [DK48238] Funding Source: Medline
Ask authors/readers for more resources
All known progesterone target cells coexpress two functionally different progesterone receptor (PR) isoforms: 120-kDa B-receptors (PR-Bm) and N-terminally truncated, 94-kDa A-receptors (PR-A). Their ratio varies in normal and malignant tissues. In human breast cancer cells, homodimers of progesterone-occupied PR-A or PR-B regulate different gene subsets. To study PR homo- and heterodimers, we constructed breast cancer cell lines in which isoform expression is controlled by an inducible system. PR-negative cells or cells that stably express one or the other isoform were used to construct five sets of cells: (i) PR-negative control cells (Y iNull), (ii) inducible PR-A cells (Y iA), (iii) inducible PR-B cells (Y iB), (iv) stable PR-B plus inducible PR-A cells (B iA), and (v) stable PR-A plus inducible PR-B cells (A iB). Expression levels of each isoform and/or the PR-A/PR-B ratios could be tightly controlled by the dose of inducer as demonstrated by immunoblotting and transcription studies. Induced PRs underwent normal progestin-dependent phosphorylation and down-regulation and regulated exogenous promoters as well as endogenous gene expression. Transcription of exogenous promoters was dependent on the PR-A/PR-B ratio, whereas transcription of endogenous genes was more complex. Finally, we have described several genes that are regulated by induced PR-A even in the absence of ligand.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available