Summary
Overexpression of neu/c-erbB-2 oncogene has been implicated in the development of
aggressive mammary cancers. To directly assaess the effect of mammary gland specific
expression of the neu proto-oncogene, transgenic mice carrying the neu protooncogene under
the transcriptional control of the MMTV promoter were established.Expression of Neu in the
mammary epithelium resulted in the development of focal mammary tumors after long latency.
Overexpression of neu was associated with elevated Neu intrinsic tyrosine kinase and
de-novo tyrosine phosphorylation of several cellular proteins. Interestingly, many of the
tumor-bearing transgenic mice developed secondary metastatic tumors to the lung.
Citation
Guy et al., 1992, Proc. Natl. Acad. Sci. U.S.A. 89, 10578-10582
Siegel et al., 1994, Mol. Cell. Biol. 14, 7068-7077
Muthuswamy et al., 1994, Mol. Cell. Biol. 14,735-743
Background
Overexpression of neu is associated with agressive breast cancer.To derive an adequate
mouse model for this disease we have generated transgenic mice expressing the neu
proto-oncogene under MMTV control.
Transgene
MMTV/ rat neu proto-oncogene
Mouse Strain : FVB/N
Phenotype
Stochastic occurence of mammary tumors which frequently metastasize to the lung.
Phenotype Image
Histology
Develop mammary tumors which resemble human comedoadenocarcinomas
Mammary development
Normal mammary gland development and regression.
Gene expression
Transgene expression is detected at low levels in virgin mammary glands but is elevated in
the normal mammary glands of multiparious female animals.Elevated levels of transgene are
detected both at the RNA and protein level in tumors.
Mechanistic implications
Induction of mammary tumors in this strain is frequiently associated with the occurence of
somatic activating mutations in the transgene (see Siegel et al., 1994). Elevated tyrosine
kinase activity is also associated with the induction of metastatic disease.
Dr. W. J. Muller
Address: 1280 Main St. West
Hamilton Ont.
Phone: 905-525-9140 ext 27306
Fax:905-521-2955
e-mail:(mullerw@mcmail.cis.mcmaster.ca)
contributed March 1996
last update: December 1998