PMID- 18470483
OWN - NLM
STAT- MEDLINE
DCOM- 20081029
LR  - 20211020
IS  - 1083-3021 (Print)
IS  - 1573-7039 (Electronic)
IS  - 1083-3021 (Linking)
VI  - 13
IP  - 2
DP  - 2008 Jun
TI  - The ADAM17-amphiregulin-EGFR axis in mammary development and cancer.
PG  - 181-94
LID - 10.1007/s10911-008-9084-6 [doi]
AB  - In order to fulfill its function of producing and delivering sufficient milk to 
      newborn mammalian offspring, the mammary gland first has to form an extensive 
      ductal network. As in all phases of mammary development, hormonal cues elicit 
      local intra- and inter-cellular signaling cascades that regulate ductal growth 
      and differentiation. Among other things, ductal development requires the 
      epidermal growth factor receptor (EGFR), its ligand amphiregulin (AREG), and the 
      transmembrane metalloproteinase ADAM17, which can cleave and release AREG from 
      the cell surface so that it may interact with its receptor. Tissue recombination 
      and transplantation studies demonstrate that EGFR phosphorylation and ductal 
      development proceed only when ADAM17 and AREG are expressed on mammary epithelial 
      cells and EGFR is present on stromal cells, and that local administration of 
      soluble AREG can rescue the development of ADAM17-deficient transplants. Thus 
      proper mammary morphogenesis requires the ADAM17-mediated release of AREG from 
      ductal epithelial cells, the subsequent activation of EGFR on stromal cells, and 
      EGFR-dependent stromal responses that in return elicit a new set of epithelial 
      responses, all culminating in the formation of a fully functional ductal tree. 
      This, however, raises new issues concerning what may act upstream, downstream or 
      in parallel with the ADAM17-AREG-EGFR axis, how it may become hijacked or 
      corrupted during the onset and evolution of cancer, and how such ill effects may 
      be confronted.
FAU - Sternlicht, Mark D
AU  - Sternlicht MD
AD  - FibroGen, Inc., 225 Gateway Boulevard, South San Francisco, CA 94080, USA, 
      msternlicht@fibrogen.com
FAU - Sunnarborg, Susan W
AU  - Sunnarborg SW
LA  - eng
GR  - R01 CA061896/CA/NCI NIH HHS/United States
GR  - CA58207/CA/NCI NIH HHS/United States
GR  - CA43793/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 CA057621-16A1/CA/NCI NIH HHS/United States
GR  - R01 CA043793-20/CA/NCI NIH HHS/United States
GR  - R01 CA061896-10/CA/NCI NIH HHS/United States
GR  - R01 CA085410-05/CA/NCI NIH HHS/United States
GR  - R01 CA085410/CA/NCI NIH HHS/United States
GR  - R01 CA057621/CA/NCI NIH HHS/United States
GR  - R01 CA043793/CA/NCI NIH HHS/United States
GR  - CA85410/CA/NCI NIH HHS/United States
GR  - CA57621/CA/NCI NIH HHS/United States
GR  - P50 CA058207-149007/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20080510
PL  - United States
TA  - J Mammary Gland Biol Neoplasia
JT  - Journal of mammary gland biology and neoplasia
JID - 9601804
RN  - 0 (AREG protein, human)
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  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - EC 3.4.24.86 (ADAM17 protein, human)
RN  - EC 3.4.24.86 (Adam17 protein, mouse)
SB  - IM
MH  - ADAM Proteins/*metabolism
MH  - ADAM17 Protein
MH  - Amphiregulin
MH  - Animals
MH  - Breast Neoplasms/*metabolism
MH  - EGF Family of Proteins
MH  - Epithelial Cells/metabolism
MH  - ErbB Receptors/*metabolism
MH  - Female
MH  - Glycoproteins/*metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*metabolism
MH  - Mammary Glands, Animal/cytology/growth & development
MH  - Mammary Glands, Human/cytology/*growth & development
MH  - Mice
MH  - Models, Biological
MH  - Morphogenesis
MH  - Stromal Cells/metabolism
PMC - PMC2723838
MID - NIHMS120060
EDAT- 2008/05/13 09:00
MHDA- 2008/10/31 09:00
PMCR- 2009/08/10
CRDT- 2008/05/13 09:00
PHST- 2008/04/21 00:00 [received]
PHST- 2008/04/23 00:00 [accepted]
PHST- 2008/05/13 09:00 [pubmed]
PHST- 2008/10/31 09:00 [medline]
PHST- 2008/05/13 09:00 [entrez]
PHST- 2009/08/10 00:00 [pmc-release]
AID - 10.1007/s10911-008-9084-6 [doi]
PST - ppublish
SO  - J Mammary Gland Biol Neoplasia. 2008 Jun;13(2):181-94. doi: 
      10.1007/s10911-008-9084-6. Epub 2008 May 10.