Reference SummaryTakayama H, Proc Natl Acad Sci U S A 1997 Jan 21;94(2):701-6
Title |
Diverse tumorigenesis associated with aberrant development in mice overexpressing hepatocyte growth factor/scatter factor. | ||||||
Authors |
Takayama H; LaRochelle WJ; Sharp R; Otsuka T; Kriebel P; Anver M ; Aaronson SA ; Merlino G | ||||||
Journal |
Proc Natl Acad Sci U S A | ||||||
Volume |
94 | ||||||
Issue |
2 | ||||||
Year |
1997 | ||||||
Pages |
701-6 | ||||||
Abstract |
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. | ||||||
Links |
J:37771 – MGI References 9012848 – National Library of Medicine/PubMed |
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Strain Notes
|
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| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| FVB/N-Tg(Mt1-Hgf)#Lmb | Adrenal gland - Cortex adenoma | Adrenal gland - Cortex |
observed |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Blood vessel hemangioma | Blood vessel |
observed |
||
| FVB/N-Tg(Mt1-Hgf)31Lmb | Blood vessel hemangiosarcoma | Liver |
observed |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Clitoral gland adenoma | Clitoral gland |
observed |
||
| FVB/N-Tg(Mt1-HGFSF)19Lmb | Connective tissue - Fibroblast fibrosarcoma | Skin |
observed |
||
| FVB/N-Tg(Mt1-Hgf)18Lmb | Connective tissue - Fibroblast fibrosarcoma | Skin |
observed |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Eye - Harderian gland adenoma | Eye - Harderian gland |
observed |
||
| FVB/N-Tg(Mt1-Hgf)37Lmb | Eye - Uvea - Melanocyte melanoma - amelanotic | Eye - Uvea - Melanocyte |
observed |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Leukocyte - Lymphoblast lymphoma - lymphoblastic | Leukocyte - Lymphoblast |
observed |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Leukocyte - Monocyte - Macrophage - Histiocyte |
observed |
||
| FVB/N-Tg(Mt1-Hgf)37Lmb | Liver hepatocellular adenoma | Liver |
observed |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Liver hepatocellular carcinoma | Liver |
observed |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Liver tumor | Liver |
observed |
||
| FVB/N-Tg(Mt1-HGFSF)22Lmb | Mammary gland adenocarcinoma | Mammary gland |
observed |
||
| FVB/N-Tg(Mt1-Hgf)27Lmb | Mammary gland adenocarcinoma | Mammary gland |
observed |
||
| FVB/N-Tg(Mt1-HGFSF)22Lmb | Mammary gland carcinoma - adenosquamous | Mammary gland |
observed |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Mammary gland hyperplasia - alveolar | Mammary gland |
observed |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Mammary gland tumor | Mammary gland |
0 - 41 |
||
| FVB/N | Mammary gland tumor | Mammary gland |
0 |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Muscle - Striated - Skeletal rhabdomyosarcoma | Muscle - Striated - Skeletal |
0 - 7.1 |
||
| FVB/N | Muscle - Striated - Skeletal rhabdomyosarcoma | Muscle - Striated - Skeletal |
0 |
||
| FVB/N-Tg(Mt1-HGFSF)22Lmb | Muscle - Striated - Skeletal rhabdomyosarcoma | Skin |
observed |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Muscle - Striated - Skeletal rhabdomyosarcoma | Peritoneum |
observed |
||
| FVB/N-Tg(Mt1-Hgf)37Lmb | Muscle - Striated - Skeletal rhabdomyosarcoma | Skin |
observed |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Nose - Olfactory gland adenocarcinoma | Nose - Olfactory gland |
observed |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Nose - Olfactory gland hyperplasia | Nose - Olfactory gland |
observed |
||
| FVB/N-Tg(Mt1-HGFSF)22Lmb | Salivary gland adenocarcinoma | Salivary gland |
observed |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Skin - Epidermis - Basal cell tumor | Skin - Epidermis - Basal cell |
observed |
||
| FVB/N-Tg(Mt1-HGFSF)22Lmb | Skin - Hair follicle tumor | Skin - Hair follicle |
observed |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Skin - Melanocyte melanoma - amelanotic | Skin - Melanocyte |
3.7 - 21 |
||
| FVB/N | Skin - Melanocyte melanoma - amelanotic | Skin - Melanocyte |
0 |
||
| FVB/N-Tg(Mt1-Hgf)37Lmb | Skin - Melanocyte melanoma - amelanotic | Skin |
observed |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Skin pilomatrixoma | Skin |
observed |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Skin squamous cell papilloma | Skin |
observed |
||
| FVB/N-Tg(Mt1-Hgf)#Lmb | Thyroid gland - Follicular cell adenoma | Thyroid gland - Follicular cell |
observed |