Regulation of Microtubule Stability in Breast Cancer
Abstract
The dynamic turnover of microtubules within the cell is essential for a number of cellular processes including progression through the cell cycle and intracellular transport. A number of chemotherapeutic drugs target microtubules and disrupt their turnover. In particular, Taxol has an antiproliferative effect due to its stabilization of microtubules, disrupting microtubule transition during the cell cycle. A gene the Private Investigator has cloned designated Opl8, has recently been demonstrated to play a regulatory role in microtubule transition through binding of the protein it encodes to tubulin dimers. Opl8 protein destabilizes microtubules and therefore has a directly opposite effect to Taxol on microtubules. We have demonstrated high level expression of Opl8 in a variety of tumors, including some primary breast cancers. We propose to determine the effect of manipulating Op18 expression in breast adenocarcinoma cell lines on microtubule stability and response to Taxol. We also propose to determine the relationship between Op18 level in primary tumors of the breast and biological characteristics of the tumors. The proposed investigations may provide novel strategies for inhibiting proliferation in breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA382840
Entities
People
- Samir M Hanash
Organizations
- University of Michigan