The overall goal of this second revision of a FIRST Award application is to characterize the tissue-specific regulation of the c-myc protooncogene using liver regeneration as a model of normal cellular proliferation. Preliminary evidence by the investigator suggests that transcription initiation of c-myc mRNA in liver and kidney following partial hepatectomy proceeds using different c-myc transcription start sites in a tissue-specific manner. Dr. Jones has also developed transgenic mouse lines which express beta-galactosidase (b-gal) under control of the human c-myc promoter and has performed pilot experiments on up-regulation of b-gal expression in kidney tissue following partial hepatectomy in c-myc/lacZ transgenic mice.
The specific aims of the current project are: 1) to characterize tissue-specific c-myc promoter utilization following partial hepatectomy using regenerating liver as a model of normal cellular proliferation; 2) to analyze tissue-specific c-myc promoter utilization in transgenic mouse lines containing the human c-myc minimal promoter region directing expression of b-gal; and 3) to characterize the functional contribution of other c-myc regulatory regions in the tissue-specific up-regulation of c-myc promoter-driven expression of b-gal and c-myc promoter utilization following partial hepatectomy in transgenic mice. These studies are intended to elucidate the molecular mechanism(s) and DNA regulatory events which govern the tissue-specific expression of the c-myc protooncogene following a proliferative stimulus in vivo.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA067239-05
Application #
2895275
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Mietz, Judy
Project Start
1996-09-01
Project End
2001-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of South Florida
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Tampa
State
FL
Country
United States
Zip Code
33612