Understanding and Targeting Cell Growth Networks in Breast Cancer
Annual rept. 17 Mar 2008-16 Mar 2009
WASHINGTON UNIV ST LOUIS MO SCHOOL OF MEDICINE
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In this first annual review, we have demonstrated a clear role for the ARF tumor suppressor in regulating ribosome biogenesis in primary mouse mammary epithelial cells. Loss of ARF results in tremendous gains in rDNA transcription and rRNA processing. This mouse will be monitored over the next year for formation of breast tumors. We have also determined that ARF induction in the absence of the Tsc1 tumor suppressor is primarily achieved through increased translation of existing ARF mRNAs. We also made significant progress in our evaluation of p68 as a novel breast cancer oncoproteins that is suppressed by ARF. We have constructed a transgenic mouse overexpressing the ARF target p68 in the breast epithelium. We have shown that p68 causes increased ribosome biogenesis and that its expression is both required for the maintenance of proliferation in breast cancer cell lines and required for the transforming effects of oncogenic Ras in the absence of ARF.
- Medicine and Medical Research