Gene Targets of C/EBPBeta Involved in Mammary Gland Development and Breast Cancer
Abstract
Targeted deletion of the bZlP transcription factor, C/EBPbeta, was shown previously to result in aberrant ductal morphogenesis and decreased lobuloalveolar development, accompanied by an altered pattern of progesterone receptor (PR) expression. Similar changes in the level and pattern of prolactin receptor (PrIR) expression were observed while screening for differentially expressed genes in C/EBPbeta KO mice. PR patterning was also altered in PrIR KO mice, as well as in mammary tissue transplants from both PrIR KO and Stat5a/b-deficient mice, with concomitant defects in hormone-induced proliferation. Downregulation of PR and activation of Stat5 phosphorylation were observed following estrogen and progesterone treatment in both C/EBPbeta KO and wildtype mice indicating that these signaling pathways were functional, despite the failure of steroid hormones to induce proliferation. IGFBP-5, lGF-Il, and IRS-I all displayed altered patterns and levels of expression in C/EBPbeta KO mice, suggestive of a change in the lGF signaling axis. In addition, SPRR2A, a marker of epidermal differentiation, and keratin 6 were misexpressed in the mammary epithelium of C/EBPbeta KO mice. Together, these data suggest that C/EBPbeta is a master regulator of mammary epithelial cell fate and that the correct spatial pattern of PR and PrIR expression is a critical determinant of hormone-regulated cell omliferation
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA408776
Entities
People
- Jeffrey M. Rosen
- Sandra L. Grimm
Organizations
- Baylor College of Medicine