Mammary Tumors Expressing the Neu Proto-oncogene Possess Elevated C-Src Tyrosine Kinase Activity

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1994 Jan 1

PMID 7903421

Citations 69

Authors

S K Muthuswamy

P M Siegel

D L Dankort

M A Webster

W J Muller

Affiliations

Soon will be listed here.

Abstract

Amplification and overexpression of the neu (c-erbB2) proto-oncogene has been implicated in the pathogenesis of 20 to 30% of human breast cancers. Although the activation of Neu receptor tyrosine kinase appears to be a pivotal step during mammary tumorigenesis, the mechanism by which Neu signals cell proliferation is unclear. Molecules bearing a domain shared by the c-Src proto-oncogene (Src homology 2) are thought to be involved in signal transduction from activated receptor tyrosine kinases such as Neu. To test whether c-Src was implicated in Neu-mediated signal transduction, we measured the activity of the c-Src tyrosine kinase in tissue extracts from either mammary tumors or adjacent mammary epithelium derived from transgenic mice expressing a mouse mammary tumor virus promoter/enhancer/unactivated neu fusion gene. The Neu-induced mammary tumors possessed six- to eightfold-higher c-Src kinase activity than the adjacent epithelium. The increase in c-Src tyrosine kinase activity was not due to an increase in the levels of c-Src but rather was a result of the elevation of its specific activity. Moreover, activation of c-Src was correlated with its ability to complex tyrosine-phosphorylated Neu both in vitro and in vivo. Together, these observations suggest that activation of the c-Src tyrosine kinase during mammary tumorigenesis may occur through a direct interaction with activated Neu.

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References

Hudziak R, Schlessinger J, Ullrich A . Increased expression of the putative growth factor receptor p185HER2 causes transformation and tumorigenesis of NIH 3T3 cells. Proc Natl Acad Sci U S A. 1987; 84(20):7159-63. PMC: 299249. DOI: 10.1073/pnas.84.20.7159. View

Di Marco E, PIERCE J, Knicley C, Di Fiore P . Transformation of NIH 3T3 cells by overexpression of the normal coding sequence of the rat neu gene. Mol Cell Biol. 1990; 10(6):3247-52. PMC: 360691. DOI: 10.1128/mcb.10.6.3247-3252.1990. View

Kypta R, Goldberg Y, Ulug E, Courtneidge S . Association between the PDGF receptor and members of the src family of tyrosine kinases. Cell. 1990; 62(3):481-92. DOI: 10.1016/0092-8674(90)90013-5. View

Paterson M, Dietrich K, Danyluk J, Paterson A, Lees A, Jamil N . Correlation between c-erbB-2 amplification and risk of recurrent disease in node-negative breast cancer. Cancer Res. 1991; 51(2):556-67. View

Soriano P, Montgomery C, Geske R, Bradley A . Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell. 1991; 64(4):693-702. DOI: 10.1016/0092-8674(91)90499-o. View

Gullick W, Love S, Wright C, Barnes D, Gusterson B, Harris A . c-erbB-2 protein overexpression in breast cancer is a risk factor in patients with involved and uninvolved lymph nodes. Br J Cancer. 1991; 63(3):434-8. PMC: 1971853. DOI: 10.1038/bjc.1991.100. View

Fazioli F, KIM U, Rhee S, Molloy C, Segatto O, Di Fiore P . The erbB-2 mitogenic signaling pathway: tyrosine phosphorylation of phospholipase C-gamma and GTPase-activating protein does not correlate with erbB-2 mitogenic potency. Mol Cell Biol. 1991; 11(4):2040-8. PMC: 359891. DOI: 10.1128/mcb.11.4.2040-2048.1991. View

van Lohuizen M, Verbeek S, Scheijen B, Wientjens E, van der Gulden H, Berns A . Identification of cooperating oncogenes in E mu-myc transgenic mice by provirus tagging. Cell. 1991; 65(5):737-52. DOI: 10.1016/0092-8674(91)90382-9. View

Arteaga C, Johnson M, Todderud G, Coffey R, Carpenter G, Page D . Elevated content of the tyrosine kinase substrate phospholipase C-gamma 1 in primary human breast carcinomas. Proc Natl Acad Sci U S A. 1991; 88(23):10435-9. PMC: 52943. DOI: 10.1073/pnas.88.23.10435. View

10.

Koch C, Moran M, Anderson D, Liu X, Mbamalu G, Pawson T . Multiple SH2-mediated interactions in v-src-transformed cells. Mol Cell Biol. 1992; 12(3):1366-74. PMC: 369570. DOI: 10.1128/mcb.12.3.1366-1374.1992. View

11.

Guy C, Cardiff R, Muller W . Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease. Mol Cell Biol. 1992; 12(3):954-61. PMC: 369527. DOI: 10.1128/mcb.12.3.954-961.1992. View

12.

Cheng H, Nishio H, Hatase O, Ralph S, Wang J . A synthetic peptide derived from p34cdc2 is a specific and efficient substrate of src-family tyrosine kinases. J Biol Chem. 1992; 267(13):9248-56. View

13.

Rijksen G, van Beurden E, Hennipman A, Michels A, Staal G . Characterization of protein tyrosine kinases from human breast cancer: involvement of the c-src oncogene product. Cancer Res. 1992; 52(17):4773-8. View

14.

Twamley G, Kypta R, Hall B, Courtneidge S . Association of Fyn with the activated platelet-derived growth factor receptor: requirements for binding and phosphorylation. Oncogene. 1992; 7(10):1893-901. View

15.

Guy C, Webster M, Schaller M, Parsons T, Cardiff R, Muller W . Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc Natl Acad Sci U S A. 1992; 89(22):10578-82. PMC: 50384. DOI: 10.1073/pnas.89.22.10578. View

16.

Songyang Z, Shoelson S, Chaudhuri M, Gish G, Pawson T, Haser W . SH2 domains recognize specific phosphopeptide sequences. Cell. 1993; 72(5):767-78. DOI: 10.1016/0092-8674(93)90404-e. View

17.

Vogel W, Lammers R, Huang J, Ullrich A . Activation of a phosphotyrosine phosphatase by tyrosine phosphorylation. Science. 1993; 259(5101):1611-4. DOI: 10.1126/science.7681217. View

18.

Courtneidge S, Dhand R, Pilat D, Twamley G, Waterfield M, Roussel M . Activation of Src family kinases by colony stimulating factor-1, and their association with its receptor. EMBO J. 1993; 12(3):943-50. PMC: 413295. DOI: 10.1002/j.1460-2075.1993.tb05735.x. View

19.

Cardiff R, Muller W . Transgenic mouse models of mammary tumorigenesis. Cancer Surv. 1993; 16:97-113. View

20.

Pepperkok R, Ansorge W, Courtneidge S . The Src family tyrosine kinases are required for platelet-derived growth factor-mediated signal transduction in NIH 3T3 cells. Proc Natl Acad Sci U S A. 1993; 90(16):7696-700. PMC: 47209. DOI: 10.1073/pnas.90.16.7696. View