C/EBPβ LIP and c-Jun synergize to regulate expression of the murine progesterone receptor

CCAAT/enhancer binding protein beta (C/EBP beta) is required for murine mammary ductal morphogenesis and alveologenesis. Progesterone is critical for proliferation and alveologenesis in adult mammary glands, and there is a similar requirement for progesterone receptor isoform B (PRB) in alveologenesis. We examined C/EBP beta regulation of PR expression. All three C/EBP beta isoforms, including typically inhibitory LIP, transactivated the PR promoter. LIP, particularly, strongly synergized with c-Jun to drive PR transcription. Endogenous C/EBP beta and cJun stimulated a PR promoter-reporter and these two factors showed promoter occupancy on the endogenous PR gene. Additionally, LIP overexpression elevated endogenous PR protein expression. In pregnancy, both PRB and the relative abundance of LIP among C/EBP beta isoforms increase. Consistent with a role in PRB expression, in vivo C/EBP beta and PR isoform A expression showed mutually exclusive localization in mammary epithelium, while C/EBP beta and PRB largely co-localized. We suggest a critical role for C/EBP beta, particularly LIP, in PRB expression.