References
Query Results -- Details
MGI Accession ID: MGI:82793
J Number: J:35344
Other Accession IDs:
Title: Synergistic interaction of the Neu proto-oncogene product and transforming growth factor alpha in the mammary epithelium of transgenic mice.
Authors: Muller WJ; Arteaga CL; Muthuswamy SK; Siegel PM; Webster MA; Cardiff RD; Meise KS; Li F; Halter SA; Coffey RJ
Journal: Mol Cell Biol
Volume: 16
Issue: 10
Date: 1996 Oct
Year: 1996
Pages: 5726-36
Review Status: Peer Reviewed
Abstract:
Transgenic mice expressing either the neu proto-oncogene or transforming growth factor (TGF-alpha) in the mammary epithelium develop spontaneous focal mammary tumors that occur after a long latency. Since the epidermal growth factor receptor (EGFR) and Neu are capable of forming heterodimers that are responsive to EGFR ligands such as TGF-alpha, we examined whether coexpression of TGF-alpha and Neu in mammary epithelium could cooperate to accelerate the onset of mammary tumors. To test this hypothesis, we interbred separate transgenic strains harboring either a mouse mammary tumor virus/TGF-alpha or a mouse mammary tumor virus/neu transgene to generate bitransgenic mice that coexpress TGF-alpha and neu in the mammary epithelium. Female mice coexpressing TGF-alpha and neu developed multifocal mammary tumors which arose after a significantly shorter latency period than either parental strain alone. The development of these mammary tumors was correlated with the tyrosine phosphorylation of Neu and the recruitment of c-Src to the Neu complex. Immunoprecipitation and immunoblot analyses with EGFR- and Neu-specific antisera, however, failed to detect physical complexes of these two receptors. Taken together, these observations suggest that Neu and TGF-alpha cooperate in mammary tumorigenesis through a mechanism involving Neu and EGFR transactivation.
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