Abstract: Overexpression and amplification of the neu (c-erbB2, ERBB2) protooncogene have
been implicated in the development of aggressive human breast cancer. To directly assess the
effect of mammary gland-specific expression of the neu protooncogene, transgenic mice carrying
unactivated neu under the transcriptional control of the mouse mammary tumor virus
promoter/enhancer were established. By contrast to the rapid tumor progression observed in
several transgenic strains carrying the activated neu transgene, expression of unactivated neu in the
mammary epithelium resulted in the development of focal mammary tumors after long latency. The
majority of the mammary tumors analyzed expressed elevated levels of neu-encoded mRNA and
protein. Overexpression of neu in the mammary tumors was also associated with elevated neu
intrinsic tyrosine kinase activity and the de novo tyrosine phosphorylation of several cellular proteins.
Interestingly, many of the tumor-bearing transgenic mice developed secondary metastatic tumors in
the lung. These observations suggest that overexpression of the unactivated neu protein can induce
metastatic disease after long latency.
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Last Updated: November 06, 1996
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