CCAAT/enhancer binding protein β negatively regulates progesterone receptor expression in human glioblastoma cells

- Human PR-B promoter region has three putative C/EBP binding sites.
- PR and C/EBPβ isoforms are differentially expressed in human glioblastoma cells.
- C/EBPβ negatively regulates PR-B expression in U251 glioblastoma cells.
- C/EBPβ participates in the estradiol-dependent expression of PR-B.

Many progesterone (P4) actions are mediated by its intracellular receptor (PR), which has two isoforms (PR-A and PR-B) differentially transcribed from separate promoters of a single gene. In glioblastomas, the most frequent and aggressive brain tumors, PR-B is the predominant isoform. In an in silico analysis we showed putative CCAAT/Enhancer Binding Protein (C/EBP) binding sites at PR-B promoter. We evaluated the role of C/EBPβ in PR-B expression regulation in glioblastoma cell lines, which expressed different ratios of PR and C/EBPβ isoforms (LAP1, LAP2, and LIP). ChIP assays showed a significant basal binding of C/EBPβ, specific protein 1 (Sp1) and estrogen receptor alpha (ERα) to PR-B promoter. C/EBPβ knockdown increased PR-B expression and treatment with estradiol (E2) reduced C/EBPβ binding to the promoter and up-regulated PR-B expression. P4 induced genes were differently regulated when CEBP/β was silenced. These data show that C/EBPβ negatively regulates PR-B expression in glioblastoma cells.