PMID- 16079154
OWN - NLM
STAT- MEDLINE
DCOM- 20051101
LR  - 20210915
IS  - 0950-1991 (Print)
IS  - 1477-9129 (Electronic)
IS  - 0950-1991 (Linking)
VI  - 132
IP  - 17
DP  - 2005 Sep
TI  - Mammary ductal morphogenesis requires paracrine activation of stromal EGFR via 
      ADAM17-dependent shedding of epithelial amphiregulin.
PG  - 3923-33
AB  - Epithelial-mesenchymal crosstalk is essential for tissue morphogenesis, but 
      incompletely understood. Postnatal mammary gland development requires epidermal 
      growth factor receptor (EGFR) and its ligand amphiregulin (AREG), which generally 
      must be cleaved from its transmembrane form in order to function. As the 
      transmembrane metalloproteinase ADAM17 can process AREG in culture and 
      Adam17(-/-) mice tend to phenocopy Egfr(-/-) mice, we examined the role of each 
      of these molecules in mammary development. Tissue recombination and 
      transplantation studies revealed that EGFR phosphorylation and ductal development 
      occur only when ADAM17 and AREG are expressed on mammary epithelial cells, 
      whereas EGFR is required stromally, and that local AREG administration can rescue 
      Adam17(-/-) transplants. Several EGFR agonists also stimulated Adam17(-/-) 
      mammary organoid growth in culture, but only AREG was expressed abundantly in the 
      developing ductal system in vivo. Thus, ADAM17 plays a crucial role in mammary 
      morphogenesis by releasing AREG from mammary epithelial cells, thereby eliciting 
      paracrine activation of stromal EGFR and reciprocal responses that regulate 
      mammary epithelial development.
FAU - Sternlicht, Mark D
AU  - Sternlicht MD
AD  - Department of Anatomy, University of California, 513 Parnassus Ave., San 
      Francisco, CA 94143-0452, USA. sternli@itsa.ucsf.edu
FAU - Sunnarborg, Susan W
AU  - Sunnarborg SW
FAU - Kouros-Mehr, Hosein
AU  - Kouros-Mehr H
FAU - Yu, Ying
AU  - Yu Y
FAU - Lee, David C
AU  - Lee DC
FAU - Werb, Zena
AU  - Werb Z
LA  - eng
GR  - P50 CA058207-15/CA/NCI NIH HHS/United States
GR  - U01 ES012801-02/ES/NIEHS NIH HHS/United States
GR  - R01 CA061896/CA/NCI NIH HHS/United States
GR  - CA58207/CA/NCI NIH HHS/United States
GR  - R01 CA085410/CA/NCI NIH HHS/United States
GR  - ES012801/ES/NIEHS NIH HHS/United States
GR  - P50 CA058207/CA/NCI NIH HHS/United States
GR  - U01 ES012801/ES/NIEHS NIH HHS/United States
GR  - R01 CA061896-06/CA/NCI NIH HHS/United States
GR  - CA85410/CA/NCI NIH HHS/United States
GR  - R01 CA057621/CA/NCI NIH HHS/United States
GR  - CA57621/CA/NCI NIH HHS/United States
GR  - R01 CA085410-01/CA/NCI NIH HHS/United States
GR  - R01 CA057621-07/CA/NCI NIH HHS/United States
GR  - CA61896/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050803
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Amphiregulin)
RN  - 0 (Areg protein, mouse)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Ligands)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - EC 3.4.24.86 (Adam17 protein, mouse)
SB  - IM
EIN - Development. 2006 Mar;133(6):1203
MH  - ADAM Proteins
MH  - ADAM17 Protein
MH  - Amphiregulin
MH  - Animals
MH  - Cells, Cultured
MH  - EGF Family of Proteins
MH  - Epithelial Cells/metabolism
MH  - ErbB Receptors/genetics/*metabolism
MH  - Female
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Developmental
MH  - Glycoproteins/deficiency/genetics/*metabolism/pharmacology
MH  - Intercellular Signaling Peptides and 
      Proteins/deficiency/genetics/*metabolism/pharmacology
MH  - Ligands
MH  - Mammary Glands, Animal/*embryology/growth & development/*metabolism
MH  - Metalloendopeptidases/genetics/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Morphogenesis/drug effects
MH  - Organoids/metabolism
MH  - *Paracrine Communication
MH  - Phosphorylation
MH  - Phosphotyrosine/metabolism
MH  - Stromal Cells/*metabolism
PMC - PMC2771180
MID - NIHMS153480
EDAT- 2005/08/05 09:00
MHDA- 2005/11/03 09:00
PMCR- 2009/11/01
CRDT- 2005/08/05 09:00
PHST- 2005/08/05 09:00 [pubmed]
PHST- 2005/11/03 09:00 [medline]
PHST- 2005/08/05 09:00 [entrez]
PHST- 2009/11/01 00:00 [pmc-release]
AID - dev.01966 [pii]
AID - 10.1242/dev.01966 [doi]
PST - ppublish
SO  - Development. 2005 Sep;132(17):3923-33. doi: 10.1242/dev.01966. Epub 2005 Aug 3.