Accession Number:

ADA532380

Title:

Understanding and Targeting Cell Growth Networks in Breast Cancer

Descriptive Note:

Annual rept. 17 Mar 2009-16 Mar 2010

Corporate Author:

WASHINGTON UNIV ST LOUIS MO SCHOOL OF MEDICINE

Personal Author(s):

Report Date:

2010-04-01

Pagination or Media Count:

16.0

Abstract:

In this second annual review, we have demonstrated that Arf-null MMECs contain unique polysome mRNA profiles, up-regulated Drosha levels, and a novel miRNA signature. We have also determined that significant crosstalk exists between the MAPK and mTOR pathways to ultimately regulate ARF mRNA translation in response to oncogenic RasV12 signals. We now understand the translational regulation of NPM. We have identified FBP1 as a key binding protein and repressor of the NPM 3-UTR. We now have mouse models aimed at understanding the complex functional interactions between ARF, NPM, and DDX5. We have generated two double knockout mouse models that help to clarify the perceived interaction of these proteins. Loss of one allele of Npm1 or Ddx5 results in a partial rescue of Arf loss with regard to tumor incidence. Taken together, these insightful findings bring us significantly closer to our goal of understanding how signaling pathways impact major tumors suppressors in the control of cell growth

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE