Gene Targets of C/EBPB Involved in Mammary Gland Development and Breast Cancer
Abstract
Targeted deletion of the bZIP 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) and estrogen receptor alpha (ERa) expression were also observed in C/EBPbeta KO mice. PR patterning was also altered in PrIR KO mice, and in mammary tissue transplants from both PrIR KO and Stat5a/b-deficient mice, with concomitant defects in hormone-induced proliferation. Along with decreased BrdU-Incorporation and decreased expression of K167 were increases in the cyclin-dependent kinase inhibitors p21 and p27. lGFBP-5, lGF-ll, and IRS-1 all displayed altered patterns and levels of expression in C/EBPbeta KO mice, suggestive of a change in the lGF signaling axis. Increased expression of markers of ductal epithelium, such as NKCC1, aquaporin 5 and keratin 8, were observed in C/EBPbeta KO glands. 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 PrlR expression is a critical determinant of hormone-regulated cell proliferation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2003
- Accession Number
- ADA420769
Entities
People
- Jeffrey M. Rosen
- Sandra L. Grimm
Organizations
- Baylor College of Medicine