Mechanisms of Ras Control of Mammary Tumor Properties in Transgenic Mice
Abstract
Expression of activated ras has been correlated with increased tumor resistance to apoptosis. For example, we have demonstrated that tumors arising in MMTV-ras mice display both low spontaneous and chemotherapy-induced apoptosis. The goal of this project is to determine the role of two major or Ras effectors, Raf1 and pI3K, in mediating tumor resistance to apoptosis. Transgenic mice expressing either constitutively active or dominant-negative forms of raf1 and PT3K are being created and characterized. In parallel, studies in cell cultures from MMTV-ras tumors are being performed to determine the effects of specific inhibitors of Raf1 or PI3K on tumor cell growth and apoptosis. We have generated one line of transgenic mice expressing activated raf1, and three lines expressing dominant-negative raf1. We have also established cell cultures from MMTV-ras tumors, and demonstrated that these cells maintain Ras protein expression and dependence upon Ras function for growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA388575
Entities
People
- Jolene J. Windle
Organizations
- Virginia Commonwealth University