Title |
Ultraviolet-Induced Signal Trasduction
|
Institution |
UNIVERSITY OF MINNESOTA TWIN CITIES, MINNEAPOLIS, MN
|
Principal Investigator |
DONG, ZIGANG
|
NCI Program Director |
Paul Okano
|
Cancer Activity |
DNA Chromosome Aberrations
|
Division |
DCB
|
Funded Amount |
$236,453
|
Project Dates |
07/01/1999 - 01/31/2009
|
Fiscal Year |
2008
|
Project Type |
Grant
|
Research Topics w/ Percent Relevance |
Cancer Types w/ Percent Relevance |
Cancer (100.0%)
Chemoprevention (25.0%)
Gene Therapy (15.0%)
Tumor Necrosis Factor (10.0%)
|
Skin (100.0%)
|
Research Type |
Cancer Initiation: Oncogenes and Tumor Suppressor Genes
Exogenous Factors in the Origin and Cause of Cancer
|
Abstract |
DESCRIPTION (provided by applicant): The hypothesis to be tested in this application is that UVB-induced activation of c-Jun N-terminal kinases (JNKs) and their downstream transcription factors/nuclear proteins plays a functional role in UVB-induced cellular apoptosis and skin carcinogenesis. Therefore these signaling molecules are potential targets for the development of chemopreventive agents to inhibit UVB-induced skin cancers. The focus of this application is to identify and study novel substrates of JNKs and their biological functions in cell transformation/carcinogenesis. The specific aims to address this hypothesis are: Specific Aim 1. To determine the role of JNKs in UVB-induced phosphorylation of Statl and Stat3. Specific Aim 2. To determine the role of JNKs in UVB-induced phosphorylation of histones H3 and H2A. Specific Aim 3. To determine the role of JNKs, Statl, Stat3 and histones H3 and H2A in UVB- or TNFalpha-induced cell cycle arrest, apoptosis or cell transformation. Specific Aim 4. To determine the role of JNKs in UVB-induced skin carcinogenesis and their potential as targets for chemoprevention of skin cancer. Such knowledge will lead to a better understanding of human skin carcinogenesis, and facilitate the design of more effective agents for chemoprevention of human skin cancer. |