Intracellular receptor (IR) activities dramatically increase at the final transition to the tumor cell in the mouse model for human sarcoma. Although the changes in receptor function are not likely to be the cause of cancer, they may be """"""""passive bystanders"""""""" that are markers of a cellular alteration that may effect both the """"""""super-activation"""""""" of the receptors and the cancer progression. In this study, we will focus on the pattern of changes in activity of the glucocorticoid receptor (GR) in cell lines that represent aggressive fibromatosis (the last pre-tumor stage) and the fibrosarcoma tumor. GR binds to specific genomic glucocorticoid response elements and triggers assembly of multicomponent, response element-specific regulatory complexes. We will define patterns of functional surfaces on GR, seeking patterns that correlate with super-activation. In addition, we shall determine the relationship between GRE sequences, GR-DNA affinities, and GR- coactivator recruitment in super-activated genes. These studies will facilitate a better understanding of cancer as a regulatory transition, and of the structure, mechanism and selectivity of cellular regulatory pathways. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32CA119471-01
Application #
7052646
Study Section
Special Emphasis Panel (ZRG1-F09 (20))
Program Officer
Lohrey, Nancy
Project Start
2006-08-31
Project End
2009-08-30
Budget Start
2006-08-31
Budget End
2007-09-01
Support Year
1
Fiscal Year
2006
Total Cost
$45,976
Indirect Cost
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143