ErbB4 signaling in the mammary gland is required for lobuloalveolar development and Stat5 activation during lactation

Frank E. Jones, Thomas Welte, Xin Yuan Fu, David F. Stern

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

Signaling by members of the epidermal growth factor receptor family plays an important role in breast development and breast cancer. Earlier work suggested that one of these receptors, ErbB4, is coupled to unique responses in this tissue. To determine the function of ErbB4 signaling in the normal mouse mammary gland, we inactivated ErbB4 signaling by expressing a COOH terminally deleted dominant-negative allele of ErbB4 (ErbB4ΔIC) as a transgene in the mammary gland. Despite the expression of ErbB4ΔIC from puberty through later stages of mammary development, an ErbB4ΔIC-specific phenotype was not observed until mid-lactation. At 12-d postpartum, lobuloalveoli expressing ErbB4ΔIC protein were condensed and lacked normal lumenal lactation products. In these lobuloalveoli, β-casein mRNA, detected by in situ hybridization, was normal. However, whey acidic protein mRNA was reduced, and α-lactalbumin mRNA was undetectable. Stat5 expression was detected by immunohistochemistry in ErbB4ΔIC-expressing tissue. However, Stat5 was not phosphorylated at Y694 and was, therefore, probably inactive. When expressed transiently in 293T cells, ErbB4 induced phosphorylation of Stat5. This phosphorylation required an intact Stat5 SH2 domain. In summary, our results demonstrate that ErbB4 signaling is necessary for mammary terminal differentiation and Stat5 activation at mid-lactation.

Original languageEnglish (US)
Pages (from-to)77-87
Number of pages11
JournalJournal of Cell Biology
Volume147
Issue number1
DOIs
StatePublished - Oct 4 1999
Externally publishedYes

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Human Mammary Glands
Lactation
Breast
Messenger RNA
Phosphorylation
Lactalbumin
src Homology Domains
HEK293 Cells
Puberty
Caseins
Transgenes
Epidermal Growth Factor Receptor
Postpartum Period
In Situ Hybridization
Immunohistochemistry
Alleles
Breast Neoplasms
Phenotype
Proteins

Keywords

  • Dominant-negative mutant
  • ErbB4
  • Mammary gland development
  • Stat5
  • Transgenic mice

ASJC Scopus subject areas

  • Cell Biology

Cite this

ErbB4 signaling in the mammary gland is required for lobuloalveolar development and Stat5 activation during lactation. / Jones, Frank E.; Welte, Thomas; Fu, Xin Yuan; Stern, David F.

In: Journal of Cell Biology, Vol. 147, No. 1, 04.10.1999, p. 77-87.

Research output: Contribution to journalArticle

Jones, Frank E. ; Welte, Thomas ; Fu, Xin Yuan ; Stern, David F. / ErbB4 signaling in the mammary gland is required for lobuloalveolar development and Stat5 activation during lactation. In: Journal of Cell Biology. 1999 ; Vol. 147, No. 1. pp. 77-87.
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