Regulation of Microtubule Stability in Breast Cancer.
Abstract
This proposal is intended to explore novel strategies that target microtubules that are relevant to breast cancer. Prior studies by the P.1. have led to the cloning of a gene designated Op18, which is expressed at high levels in breast cancer. Op18 plays a regulatory role in microtubule transition through binding to tubulin dimers. The identification of Op18 as a regulator of microtubules is of significance in view of the importance of microtubules and their regulated growth or shrinkage in a number of essential cellular processes including progression through the cell cycle, maintenance of cell shape, and intracellular transport and in view of the relevance of microtubules as targets of breast cancer therapy. This project has two objectives. One is to test the hypothesis that Op18 levels as well as its phosphorylation status affect the ability of breast cancer cells to progress through the cell cycle and to proliferate. The second objective is to test the hypothesis that Op18 exerts a regulatory role on microtubule assembly that is dependent on both Opl8 level and phosphorylation status. In the past year we have obtained evidence that Op18 microtubule destabilizing activity is dependent on phosphorylation. We have also obtained evidence of substantial variability in both Opl8 and of tubulin contents in breast tumors and cell lines. Both in vitro and transgenic mouse models have been - developed that should allow in the coming year assessment of the role of Op18 levels in proliferation and of the growth properties of transfected breast cancer cells and of their response to taxol.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADA360324
Entities
People
- Samir M Hanash
Organizations
- University of Michigan