Impact of Disrupted Brca2 Protein-Protein Interactions on DNA Repair and Tumorigenesis
Annual summary 1 Jul 2001-30 Jun 2002
DREXEL UNIV PHILADELPHIA PA
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In this report, we have investigated the effects of overexpression of active Ras within the mammary epithelium. Using the tetracycline-inducible system, we have generated a line of mice which, when also bearing rtTA transgene expressed under control of the MMTV LTR, inducibly express active H-Ras in the mammary epithelium in response to the drug doxycycline. We have shown that the mammary epithelium undergoes a large amount of proliferation in response to Ras Removal of doxycycline abrogates the hyperplastic phenotype and restores a normal gland within 60 days. We have also shown that pathways downstream of Ras are activated, such as the RafMEKMAPK pathway. Furthermore, the pl9p53p21 pathway is also activated in response to Ras.
- Medicine and Medical Research