Reference SummaryGuy CT, Genes Dev 1994 Jan;8(1):23-32
Title |
Activation of the c-Src tyrosine kinase is required for the induction of mammary tumors in transgenic mice. | ||||||||
Authors |
Guy CT; Muthuswamy SK; Cardiff RD; Soriano P; Muller WJ | ||||||||
Journal |
Genes Dev | ||||||||
Volume |
8 | ||||||||
Issue |
1 | ||||||||
Year |
1994 | ||||||||
Pages |
23-32 | ||||||||
Abstract |
Transgenic mice expressing the polyomavirus (PyV) middle T oncogene in the mammary epithelium develop multifocal mammary tumors that metastasize with high frequency. The potent transforming activity of PyV middle T antigen can, in part, be attributed to its ability to associate with and to activate a number of c-Src family tyrosine kinases (c-Src, c-Yes, and Fyn). As a first step toward assessing the role of individual c-Src family tyrosine kinases in PyV middle T antigen-induced mammary tumorigenesis, we have crossed transgenic mice carrying the mouse mammary tumor virus (MMTV)/PyV middle T antigen fusion gene with mice bearing a disrupted c-src proto-oncogene. In contrast to the rapid tumor progression seen in the original MMTV/PyV middle T antigen strains, mice expressing the transgene in the absence of functional c-Src rarely developed mammary tumors. After long latency, these mice did eventually develop abnormal hyperplastic mammary tissue. This growth disturbance was correlated with elevated expression of the PyV middle T antigen and the activation of the PyV middle T antigen-associated c-Yes tyrosine kinase. However, transgenic mice expressing the PyV middle T antigen in the mammary epithelium of wild-type or Yes-deficient mice developed multifocal mammary tumors with comparable kinetics. Taken together, these findings suggest that c-Src tyrosine kinase activity is required for PyV middle T antigen-induced mammary tumorigenesis and also illustrate an in vivo genetic approach to the dissection of mitogenic signal transduction pathways. | ||||||||
Links |
J:72125 – MGI References 7507074 – National Library of Medicine/PubMed |
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Strain Notes
|
Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
---|---|---|---|---|---|
[not specified]-Tg(MMTV-PyVT)634Mul | Mammary gland adenocarcinoma | Mammary gland |
100 |
||
[not specified]-Srctm1Sor/+ Tg(MMTV-PyVT)634Mul | Mammary gland adenocarcinoma | Mammary gland |
100 |
||
[not specified]-Srctm1Sor Tg(MMTV-PyVT)634Mul | Mammary gland adenocarcinoma | Mammary gland |
0 - 8.3 |
||
[not specified]-Tg(MMTV-PyVT)634Mul | Mammary gland adenocarcinoma | Mammary gland |
100 |
||
[not specified]-Tg(MMTV-PyVT)634Mul Yes1tm#Sor/+ | Mammary gland adenocarcinoma | Mammary gland |
100 |
||
[not specified]-Tg(MMTV-PyVT)634Mul Yes1tm#Sor | Mammary gland adenocarcinoma | Mammary gland |
100 |
||
FVB/N-Tg(MMTV-PyVT)121Mul | Mammary gland adenocarcinoma | Mammary gland |
observed |
||
FVB/N-Tg(MMTV-PyVT)634Mul | Mammary gland adenocarcinoma | Mammary gland |
observed |
||
FVB/N-Tg(MMTV-PyVT)668Mul | Mammary gland adenocarcinoma | Mammary gland |
observed |
||
[not specified]-Srctm1Sor Tg(MMTV-PyVT)634Mul | Mammary gland hyperplasia | Mammary gland |
observed |