C/EBPβ, but not C/EBPα, is essential for ductal morphogenesis, lobuloalveolar proliferation, and functional differentiation in the mouse mammary gland

Tiffany Seagroves, Susanne Krnacik, Brian Raught, Jason Gay, Bonnie Burgess-Beusse, Gretchen J. Darlington, Jeffrey M. Rosen

Research output: Contribution to journalArticle

207 Citations (Scopus)

Abstract

The CCAAT/enhancer binding proteins (C/EBPs) are differentially expressed throughout mammary gland development and interact with binding sites within the promoter of a milk protein gene, β-casein. The specific roles of C/EBPβ and C/EBPα in mouse mammary gland development and differentiation have been investigated in mice that carry targeted deletions of these genes. C/EBPβ(-/-) virgin mice exhibited cystic, enlarged mammary ducts with decreased secondary branching. Transplantation of C/EBPβ(-/-) mammary epithelium into the cleared mammary fat pads of nude mice confirmed that this defect in ductal morphogenesis was intrinsic to the epithelium. When treated with estrogen/progesterone (E+P) to simulate pregnancy, C/EBPβ(-/-) mammary glands displayed only limited lobuloalveolar development and ductal side branching. Primary mammary epithelial cells obtained from E+P-treated C/EBPβ(-/-) mice that were cultured on extracellular matrix gels did not functionally differentiate in response to lactogenic hormones despite their organization into three-dimensional structures. Expression of β- casein protein was inhibited 85%-100% and whey acidic protein (WAP) was undetectable. In contrast, no detectable alterations in mammary development or β-casein expression were observed in mammary outgrowths derived from newborn C/EBPα(-/-) mammary epithelium transplanted into the cleared mammary fat pads of syngeneic hosts. These results demonstrate that C/EBPβ, but not C/EBPα, is required for ductal morphogenesis, lobuloalveolar development, and functional differentiation of mammary epithelial cells.

Original languageEnglish (US)
Pages (from-to)1917-1928
Number of pages12
JournalGenes and Development
Volume12
Issue number12
DOIs
StatePublished - Jun 15 1998
Externally publishedYes

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CCAAT-Enhancer-Binding Proteins
Human Mammary Glands
Morphogenesis
Breast
Caseins
Epithelium
Adipose Tissue
Epithelial Cells
Milk Proteins
Gene Deletion
Nude Mice
Extracellular Matrix
Progesterone
Estrogens
Transplantation
Gels
Binding Sites
Hormones

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

Cite this

C/EBPβ, but not C/EBPα, is essential for ductal morphogenesis, lobuloalveolar proliferation, and functional differentiation in the mouse mammary gland. / Seagroves, Tiffany; Krnacik, Susanne; Raught, Brian; Gay, Jason; Burgess-Beusse, Bonnie; Darlington, Gretchen J.; Rosen, Jeffrey M.

In: Genes and Development, Vol. 12, No. 12, 15.06.1998, p. 1917-1928.

Research output: Contribution to journalArticle

Seagroves, Tiffany ; Krnacik, Susanne ; Raught, Brian ; Gay, Jason ; Burgess-Beusse, Bonnie ; Darlington, Gretchen J. ; Rosen, Jeffrey M. / C/EBPβ, but not C/EBPα, is essential for ductal morphogenesis, lobuloalveolar proliferation, and functional differentiation in the mouse mammary gland. In: Genes and Development. 1998 ; Vol. 12, No. 12. pp. 1917-1928.
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abstract = "The CCAAT/enhancer binding proteins (C/EBPs) are differentially expressed throughout mammary gland development and interact with binding sites within the promoter of a milk protein gene, β-casein. The specific roles of C/EBPβ and C/EBPα in mouse mammary gland development and differentiation have been investigated in mice that carry targeted deletions of these genes. C/EBPβ(-/-) virgin mice exhibited cystic, enlarged mammary ducts with decreased secondary branching. Transplantation of C/EBPβ(-/-) mammary epithelium into the cleared mammary fat pads of nude mice confirmed that this defect in ductal morphogenesis was intrinsic to the epithelium. When treated with estrogen/progesterone (E+P) to simulate pregnancy, C/EBPβ(-/-) mammary glands displayed only limited lobuloalveolar development and ductal side branching. Primary mammary epithelial cells obtained from E+P-treated C/EBPβ(-/-) mice that were cultured on extracellular matrix gels did not functionally differentiate in response to lactogenic hormones despite their organization into three-dimensional structures. Expression of β- casein protein was inhibited 85{\%}-100{\%} and whey acidic protein (WAP) was undetectable. In contrast, no detectable alterations in mammary development or β-casein expression were observed in mammary outgrowths derived from newborn C/EBPα(-/-) mammary epithelium transplanted into the cleared mammary fat pads of syngeneic hosts. These results demonstrate that C/EBPβ, but not C/EBPα, is required for ductal morphogenesis, lobuloalveolar development, and functional differentiation of mammary epithelial cells.",
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