Guy CT; Webster MA; Schaller M; Parsons TJ; Cardiff RD; Muller WJ. Expression of the neu protooncogene in the mammary epithelium of
transgenic mice induces metastatic disease. Proceedings of the National Academy of Sciences of the United States of America, 1992 Nov
15, 89(22):10578-82. (UI: 93066287)
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.