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

Strain Notes

Strain Note
[not specified]-Srctm1Sor Tg(MMTV-PyVT)634Mul Transgene was expressed in mammary glands from multiparous mice.
[not specified]-Srctm1Sor/+ Tg(MMTV-PyVT)634Mul The transgene was expressed in mammary glands from multiparous mice.
[not specified]-Tg(MMTV-PyVT)634Mul The transgene was expressed in mammary glands from multiparous mice.

Models
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