PMID- 17448457
OWN - NLM
STAT- MEDLINE
DCOM- 20070719
LR  - 20181113
IS  - 0012-1606 (Print)
IS  - 1095-564X (Electronic)
IS  - 0012-1606 (Linking)
VI  - 306
IP  - 1
DP  - 2007 Jun 1
TI  - The MAPK(ERK-1,2) pathway integrates distinct and antagonistic signals from 
      TGFalpha and FGF7 in morphogenesis of mouse mammary epithelium.
PG  - 193-207
AB  - Transforming growth factor-alpha (TGFalpha) and fibroblast growth factor-7 (FGF7) 
      exhibit distinct expression patterns in the mammary gland. Both factors signal 
      through mitogen-activated kinase/extracellular regulated kinase-1,2 
      (MAPK(ERK1,2)); however, their unique and/or combined contributions to mammary 
      morphogenesis have not been examined. In ex vivo mammary explants, we show that a 
      sustained activation of MAPK(ERK1,2) for 1 h, induced by TGFalpha, was necessary 
      and sufficient to initiate branching morphogenesis, whereas a transient 
      activation (15 min) of MAPK(ERK1,2), induced by FGF7, led to growth without 
      branching. Unlike TGFalpha, FGF7 promoted sustained proliferation as well as 
      ectopic localization of, and increase in, keratin-6 expressing cells. The 
      response of the explants to FGF10 was similar to that to FGF7. Simultaneous 
      stimulation by FGF7 and TGFalpha indicated that the FGF7-induced MAPK(ERK1,2) 
      signaling and associated phenotypes were dominant: FGF7 may prevent branching by 
      suppression of two necessary TGFalpha-induced morphogenetic effectors, matrix 
      metalloproteinase-3 (MMP-3/stromelysin-1), and fibronectin. Our findings indicate 
      that expression of morphogenetic effectors, proliferation, and cell-type 
      decisions during mammary organoid morphogenesis are intimately dependent on the 
      duration of activation of MAPK(ERK1,2) activation.
FAU - Fata, Jimmie E
AU  - Fata JE
AD  - Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 
      94720, USA. jefata@lbl.gov <jefata@lbl.gov>
FAU - Mori, Hidetoshi
AU  - Mori H
FAU - Ewald, Andrew J
AU  - Ewald AJ
FAU - Zhang, Hui
AU  - Zhang H
FAU - Yao, Evelyn
AU  - Yao E
FAU - Werb, Zena
AU  - Werb Z
FAU - Bissell, Mina J
AU  - Bissell MJ
LA  - eng
GR  - U01 ES012801-04S3/ES/NIEHS NIH HHS/United States
GR  - R01 CA057621-13/CA/NCI NIH HHS/United States
GR  - R01 CA057621-12/CA/NCI NIH HHS/United States
GR  - ES012801/ES/NIEHS NIH HHS/United States
GR  - R01 CA057621-11/CA/NCI NIH HHS/United States
GR  - R01 CA057621-15/CA/NCI NIH HHS/United States
GR  - HL-007731/HL/NHLBI NIH HHS/United States
GR  - U01 ES012801/ES/NIEHS NIH HHS/United States
GR  - T32 HL007731/HL/NHLBI NIH HHS/United States
GR  - R01 CA057621-14/CA/NCI NIH HHS/United States
GR  - R01 CA057621/CA/NCI NIH HHS/United States
GR  - CA57621/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, Non-P.H.S.
DEP - 20070316
PL  - United States
TA  - Dev Biol
JT  - Developmental biology
JID - 0372762
RN  - 0 (Fgf7 protein, mouse)
RN  - 0 (Fibronectins)
RN  - 0 (Gels)
RN  - 0 (Keratin-6)
RN  - 0 (Transforming Growth Factor alpha)
RN  - 126469-10-1 (Fibroblast Growth Factor 7)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - Cell Polarity
MH  - Cell Proliferation
MH  - Epithelium/chemistry/growth & development/metabolism
MH  - Extracellular Matrix/metabolism
MH  - Female
MH  - Fibroblast Growth Factor 7/pharmacology/*physiology
MH  - Fibronectins/metabolism
MH  - Gels/chemistry
MH  - Keratin-6/analysis/metabolism
MH  - Mammary Glands, Animal/drug effects/enzymology/*growth & development
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/*metabolism
MH  - *Morphogenesis/drug effects
MH  - Organ Culture Techniques
MH  - Phosphorylation
MH  - Signal Transduction
MH  - Transforming Growth Factor alpha/pharmacology/*physiology
PMC - PMC2763137
MID - NIHMS74395
EDAT- 2007/04/24 09:00
MHDA- 2007/07/20 09:00
PMCR- 2009/10/18
CRDT- 2007/04/24 09:00
PHST- 2006/10/03 00:00 [received]
PHST- 2007/03/09 00:00 [revised]
PHST- 2007/03/09 00:00 [accepted]
PHST- 2007/04/24 09:00 [pubmed]
PHST- 2007/07/20 09:00 [medline]
PHST- 2007/04/24 09:00 [entrez]
PHST- 2009/10/18 00:00 [pmc-release]
AID - S0012-1606(07)00195-9 [pii]
AID - 10.1016/j.ydbio.2007.03.013 [doi]
PST - ppublish
SO  - Dev Biol. 2007 Jun 1;306(1):193-207. doi: 10.1016/j.ydbio.2007.03.013. Epub 2007 
      Mar 16.