Impact of Disrupted Brca2 Protein-Protein Interactions on DNA Repair and Tumorigenesis.

摘要

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 Raf/MEK/MAPK pathway. Furthermore, the pl9/p53/p21 pathway is also activated in response to Ras.