Reference SummaryGallego MI, Oncogene 2003 Nov 20;22(52):8498-508
Title |
Targeted expression of HGF/SF in mouse mammary epithelium leads to metastatic adenosquamous carcinomas through the activation of multiple signal transduction pathways. | ||||
Authors |
Gallego MI; Bierie B; Hennighausen L | ||||
Journal |
Oncogene | ||||
Volume |
22 | ||||
Issue |
52 | ||||
Year |
2003 | ||||
Pages |
8498-508 | ||||
Abstract |
Overexpression of hepatocyte growth factor (HGF), also called scatter factor (SF), and its receptor c-Met are associated with poor prognosis for cancer patients. In particular, breast cancer cells can produce HGF that acts in a paracrine as well as in an autocrine manner. Therefore, HGF and c-Met are putative targets for cancer therapy. To explore HGF/c-Met signaling in breast cancer, we have generated transgenic mice expressing HGF specifically in mammary epithelium under the transcriptional control of the whey acidic protein (WAP) gene promoter. WAP-HGF transgenic females developed hyperplastic ductal trees and multifocal invasive tumors after several pregnancies, some of which progressed to lung metastases. Tumors produced HGF and displayed phosphorylated c-Met, which correlated with increased Akt as well as c-myc activation. A high growth rate, as demonstrated by Ki67 nuclear antigen staining, and a lack of progesterone receptor were characteristic of the tumors. Immunohistochemical analysis revealed areas of osteopontin (Opn) expression in WAP-HGF tumors and lung metastases in agreement with a previously reported role for Opn in invasive growth. We suggest that these mice may serve as a new breast cancer model for the evaluation of the effects of unscheduled HGF expression in breast cancer. | ||||
Links |
J:86776 – MGI References 14627990 – 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(Wap-Hgf)402Mig | Mammary gland adenocarcinoma | Mammary gland |
20 - 89 |
||
| FVB/N-Tg(Wap-Hgf)402Mig | Mammary gland hyperplasia | Mammary gland |
observed |
||
| FVB/N | Mammary gland hyperplasia | Mammary gland |
0 |
||
| FVB/N-Tg(Wap-Hgf)402Mig | Mammary gland keratoacanthoma | Mammary gland |
observed |