The C/EBPbeta transcription factor regulates epithelial cell proliferation and differentiation in the mammary gland.
Studies of C/EBPbeta-deficient mice have demonstrated a pivotal role for this transcription factor in hematopoiesis, adipogenesis, and ovarian function. Here we show that C/EBPbeta is also essential for normal development and function of the mammary gland. Ductal morphogenesis in virgin C/EBPbeta-deficient mice was disrupted, with ducts displaying reduced growth and branching. To distinguish whether the effect of C/EBPbeta deficiency on mammary epithelium is indirect or cell autonomous, we performed ovarian and mammary gland transplants. Transplants of wild-type ovaries into mutant females partially restored ductal morphogenesis during puberty but failed to support mammopoiesis during pregnancy. At term, mutant mice harboring wild-type ovaries exhibited reduced alveolar proliferation and impaired epithelial cell differentiation, including a complete absence of milk protein expression. Mammary gland transplant experiments demonstrated that development of C/EBPbeta-deficient epithelium was defective within a wild-type stroma and host background. Cell proliferation during pregnancy was reduced and differentiation, as measured by the activity of milk protein genes, was inhibited. However, wild-type epithelium developed in a C/EBPbeta-deficient stroma. Thus, C/EBPbeta plays an essential, cell autonomous role in the proliferation and differentiation of mammary secretory epithelial cells and is required for the activation of milk protein genes.
Robinson
G W
GW
Laboratory of Genetics and Physiology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, Maryland 20892-1812, USA. gertrar@bdg10.niddk.nih.gov
Johnson
P F
PF
Hennighausen
L
L
Sterneck
E
E
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism / Q000637:transplantation; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005796:Genes / Q000235:genetics; D008297:Male; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000254:growth & development* / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008894:Milk Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010053:Ovary / Q000502:physiology / Q000637:transplantation; D011247:Pregnancy; D017154:Stromal Cells; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors