PMID- 10508857
OWN - NLM
STAT- MEDLINE
DCOM- 19991104
LR  - 20191023
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 147
IP  - 1
DP  - 1999 Oct 4
TI  - ErbB4 signaling in the mammary gland is required for lobuloalveolar development
      and Stat5 activation during lactation.
PG  - 77-88
AB  - 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 (ErbB4DeltaIC) as a transgene in the mammary
      gland. Despite the expression of ErbB4DeltaIC from puberty through later stages
      of mammary development, an ErbB4DeltaIC-specific phenotype was not observed until
      mid-lactation. At 12-d postpartum, lobuloalveoli expressing ErbB4DeltaIC protein 
      were condensed and lacked normal lumenal lactation products. In these
      lobuloalveoli, beta-casein mRNA, detected by in situ hybridization, was normal.
      However, whey acidic protein mRNA was reduced, and alpha-lactalbumin mRNA was
      undetectable. Stat5 expression was detected by immunohistochemistry in
      ErbB4DeltaIC-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.
FAU - Jones, F E
AU  - Jones FE
AD  - Department of Pathology, BML 342, Yale University School of Medicine, New Haven, 
      Connecticut 06520-8023, USA.
FAU - Welte, T
AU  - Welte T
FAU - Fu, X Y
AU  - Fu XY
FAU - Stern, D F
AU  - Stern DF
LA  - eng
GR  - R01CA45708/CA/NCI NIH HHS/United States
GR  - R01GM55590/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Milk Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Trans-Activators)
RN  - EC 2.7.10.1 (ERBB4 protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Erbb4 protein, mouse)
RN  - EC 2.7.10.1 (Receptor, ErbB-4)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - ErbB Receptors/genetics/*metabolism
MH  - Female
MH  - Gene Expression Regulation, Developmental
MH  - Humans
MH  - *Lactation
MH  - Mammary Glands, Animal/anatomy & histology/cytology/*growth &
      development/*metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Milk Proteins/genetics/metabolism
MH  - Phosphorylation
MH  - Precipitin Tests
MH  - Pregnancy
MH  - RNA, Messenger/analysis/genetics
MH  - Receptor, ErbB-4
MH  - STAT5 Transcription Factor
MH  - Sequence Deletion
MH  - *Signal Transduction
MH  - Trans-Activators/*metabolism
MH  - Transgenes/genetics
MH  - src Homology Domains
PMC - PMC2164978
EDAT- 1999/10/06 00:00
MHDA- 1999/10/06 00:01
CRDT- 1999/10/06 00:00
PHST- 1999/10/06 00:00 [pubmed]
PHST- 1999/10/06 00:01 [medline]
PHST- 1999/10/06 00:00 [entrez]
AID - 10.1083/jcb.147.1.77 [doi]
PST - ppublish
SO  - J Cell Biol. 1999 Oct 4;147(1):77-88. doi: 10.1083/jcb.147.1.77.