Role of Dynein Light Chain 1 in Tamoxifen Resistance in Breast Cancer
Abstract
My proposal is designed to discover the role of DLC1 in the action of tamoxifen in breast cancer and the involvement of its phosphorylation by Pak1 in this context. The hypothesis is that tamoxifen stimulates the expression and function of DLC1, and that deregulation of DLC1 stimulates the expression of ER-target genes and leading to an enhanced cell survival, and inability of tamoxifen to suppress the action of estrogen in breast cancer cells. We plan to investigate the following points. (1) Study the mechanisms of tamoxifen regulation of DLC1 expression in breast cancer cells. (2) Determine the functional consequences of tamoxifen regulation of DLC1 expression upon the biology of breast cancer cells. (3) Define the effects of DLC1-WT and DLC1-Ser-88-Ala mutant in a transgenic murine model. To date, we found that overexpression of DLC1 caused mammary alveolar hyperplasia, an early stage of mammary neoplasia. Moreover, mammary glands from MMTV-DLC1-Ser88Ala mice had accelerated involution. Together, these results suggest that deregulated DLC1 could alter mammary gland development and its phosphorylation by Pak1 is essential for its function.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2007
- Accession Number
- ADA469357
Entities
People
- Chunying Song
Organizations
- The University of Texas MD Anderson Cancer Center