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Tissue Specific Activation and Inactivation of the Neu Proto-Oncogene in Transgenic Mice Using Cre Recombinase

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Annual summary rept. 1 Sep 1999-1 Sep 2000

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In human breast cancer, 20 to 30 of human breast cancers amplify and overexpress the Neu proto-oncogene. To fully elucidate the role of this gene in normal development and breast cancer, we have designed and implemented experiments to test the gain and loss of function of Neu in the mouse mammary epithelium. Since the knockout of Neu results in embryonic lethality, the null mutation is not easily examined. To examine mammary development in the absence of Neu, we have knocked Neu out specifically in the mammary epithelium through the use of Cre Recombinase. The preliminary analysis has not revealed a phenotype, however we have not yet examined lactation and regression. To address the role of Neu in mammary tumorigenesis, I have conditionally placed NeuNT under the control of the endogenous promoter specifically in the mammary gland. These mice express NeuNT during mammary gland development, resulting in abnormal mammary gland development, characterized by numerous side branches and lobuloalveolar side buds. Tumorigenesis in this strain occurs in 50 of the afflicted female by 13.52 months and is associated with both membrane and cytoplasmic immunoreactivity for NeuNT. Interestingly, there is both amplification and overexpression of the NeuNT allele in this tumor model.

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  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

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