P/CAF Function in Transcriptional Activation by Steroid Hormone Receptors and Mammary Cell Proliferation
Abstract
The purpose of this research is to investigate the role of histone acetyltransferases in the estrogen responses and the development and progression of breast tumors. Experiments were initially focused on one of these enzymes, PCAF. We have completed the major goals outlined in our Statement of Work for the first two years, which encompass the bulk of our Specific Aims 1-4. Our studies have revealed that another acetylase, GCN5, is very highly related in both structure in and function to PCAF. However, loss of these two enzymes has dramatically different effects in mice. PCAF null mice are viable, fertile, and exhibit no defects in estrogen dependent processes. However loss of GCN5 leads to embryonic lethality due to loss of increased programmed cell death of mesodermal tissues. Moreover, GCN5 is genetically linked to BRCA1 and provides a candidate for a tumor suppressor gene associated with spontaneous breast and ovarian cancers. These results suggest that GCN5 is important to regulation of apoptosis and may play a role in tumor development. Experiments in the coming year will further examine the functions of GCN5 and PCAF in mouse development, apoptosis, and tumor formation or progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA375129
Entities
People
- Sharon Y. Roth
Organizations
- The University of Texas MD Anderson Cancer Center