The inhibitors of DNA or differentiation (Id proteins), members of the helix-loop-helix transcription factor family, act in a dominant negative fashion to control cell cycle and differentiation by dimerizing and inhibiting the function of the basic helix-loop helix (bHLH) transcription factors. We hypothesize that removal of 3 out of 4 copies of the Id1 and Id3 genes, and the resultant deficiency of Id, disrupts normal bHLH transcription factor regulation, thus allowing the formation of normally regulated or restricted protein-DNA complexes. The deregulation of bHLH transcription factors may result in the inhibited tumor-associated angiogenesis phenotype previously described in these mice. Therefore, the major goal of this study is to identify and characterize the protein-DNA complexes and the interactions that occur in spontaneous tumors as a result of the deficiency in Id and to determine changes in gene expression. To perform these studies, Id 3 out of 4 copies knocked out mice (Id1 +/ Id3-/-) will be crossbred with the p53-/- murine tumor model. The resulting mice will be a source of tissue that will be examined histologically and on a molecular and biochemical basis to identify novel interactions and gene expression that the absence of Id allows. These studies will help us understand the role of Ids in regulating tumor-associated angiogenesis and may identify new targets for use in blocking tumor vascularization and designing more specific anti-angiogenic drugs.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31CA097517-02
Application #
6619613
Study Section
Special Emphasis Panel (ZRG1-F05 (29))
Program Officer
Bini, Alessandra M
Project Start
2002-08-01
Project End
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
2
Fiscal Year
2003
Total Cost
$37,741
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Type
Other Domestic Higher Education
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065