PMID- 9012848
OWN - NLM
STAT- MEDLINE
DCOM- 19970306
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 94
IP  - 2
DP  - 1997 Jan 21
TI  - Diverse tumorigenesis associated with aberrant development in mice overexpressing 
      hepatocyte growth factor/scatter factor.
PG  - 701-6
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a mesenchymally derived, 
      multifunctional paracrine regulator possessing mitogenic, motogenic, and 
      morphogenetic activities in cultured epithelial cells containing its tyrosine 
      kinase receptor, Met. c-met has been implicated in oncogenesis through 
      correlation of expression with malignant phenotype in specific cell lines and 
      tumors. Paradoxically, however, HGF/SF can also inhibit the growth of some tumor 
      cells. To elucidate the oncogenic role of HGF/SF in vivo, transgenic mice were 
      created such that HGF/SF was inappropriately targeted to a variety of tissues. 
      HGF/SF transgenic mice developed a remarkably broad array of histologically 
      distinct tumors of both mesenchymal and epithelial origin. Many neoplasms arose 
      from tissues exhibiting abnormal development, including the mammary gland, 
      skeletal muscle, and melanocytes, suggesting a functional link between mechanisms 
      regulating morphogenesis and those promoting tumorigenesis. Most neoplasms, 
      especially melanomas, demonstrated overexpression of both the HGF/SF transgene 
      and endogenous c-met, and had enhanced Met kinase activity, strongly suggesting 
      that autocrine signaling broadly promotes tumorigenesis. Thus, subversion of 
      normal mesenchymal-epithelial paracrine regulation through the forced 
      misdirection of HGF/SF expression induces aberrant morphogenesis and subsequent 
      malignant transformation of cells of diverse origin.
FAU - Takayama, H
AU  - Takayama H
AD  - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 
      20892-4255, USA.
FAU - LaRochelle, W J
AU  - LaRochelle WJ
FAU - Sharp, R
AU  - Sharp R
FAU - Otsuka, T
AU  - Otsuka T
FAU - Kriebel, P
AU  - Kriebel P
FAU - Anver, M
AU  - Anver M
FAU - Aaronson, S A
AU  - Aaronson SA
FAU - Merlino, G
AU  - Merlino G
LA  - eng
GR  - 1-T32-EY07131-03/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 9038-94-2 (Metallothionein)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Epithelial Cells
MH  - Gene Expression
MH  - Gene Expression Regulation, Developmental
MH  - Hepatocyte Growth Factor/*physiology
MH  - Mesoderm/cytology
MH  - Metallothionein/genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Morphogenesis
MH  - Neoplasms, Experimental/*genetics
MH  - Proto-Oncogene Proteins c-met
MH  - Receptor Protein-Tyrosine Kinases/metabolism
PMC - PMC19577
EDAT- 1997/01/21 00:00
MHDA- 1997/01/21 00:01
PMCR- 1997/07/21
CRDT- 1997/01/21 00:00
PHST- 1997/01/21 00:00 [pubmed]
PHST- 1997/01/21 00:01 [medline]
PHST- 1997/01/21 00:00 [entrez]
PHST- 1997/07/21 00:00 [pmc-release]
AID - 1934 [pii]
AID - 10.1073/pnas.94.2.701 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):701-6. doi: 10.1073/pnas.94.2.701.