PMID- 7507074 OWN - NLM STAT- MEDLINE DCOM- 19940223 LR - 20190516 IS - 0890-9369 (Print) IS - 0890-9369 (Linking) VI - 8 IP - 1 DP - 1994 Jan TI - Activation of the c-Src tyrosine kinase is required for the induction of mammary tumors in transgenic mice. PG - 23-32 AB - 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. FAU - Guy, C T AU - Guy CT AD - Institute for Molecular Biology and Biotechnology, McMaster University, Hamilton, Ontario, Canada. FAU - Muthuswamy, S K AU - Muthuswamy SK FAU - Cardiff, R D AU - Cardiff RD FAU - Soriano, P AU - Soriano P FAU - Muller, W J AU - Muller WJ LA - eng GR - R01-CA-S4285/CA/NCI 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 - Genes Dev JT - Genes & development JID - 8711660 RN - 0 (Antigens, Polyomavirus Transforming) RN - 0 (Proto-Oncogene Proteins) RN - EC 2.7.10.2 (Proto-Oncogene Proteins c-yes) RN - EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src)) RN - EC 2.7.10.2 (Yes1 protein, mouse) RN - EC 2.7.10.2 (src-Family Kinases) SB - IM MH - Animals MH - Antigens, Polyomavirus Transforming/genetics MH - Enzyme Activation MH - Mammary Neoplasms, Experimental/*etiology/genetics MH - Mice MH - Mice, Transgenic MH - Oncogenes MH - Proto-Oncogene Proteins/physiology MH - Proto-Oncogene Proteins c-yes MH - Proto-Oncogene Proteins pp60(c-src)/*metabolism/physiology MH - *src-Family Kinases EDAT- 1994/01/01 00:00 MHDA- 1994/01/01 00:01 CRDT- 1994/01/01 00:00 PHST- 1994/01/01 00:00 [pubmed] PHST- 1994/01/01 00:01 [medline] PHST- 1994/01/01 00:00 [entrez] AID - 10.1101/gad.8.1.23 [doi] PST - ppublish SO - Genes Dev. 1994 Jan;8(1):23-32. doi: 10.1101/gad.8.1.23.