B-cell cancers such as CLL (Chronic Lymphocytic Leukemia), FL (Follicular Lymphoma) and DLBCL (Diffuse Large B-cell Lymphoma) account for the majority of hematological malignancies in the Western World. These cancers feature a dysregulated PIS kinase pathway, which is a pivotal signaling pathway that promotes cellular proliferation and survival, and enhances adhesion and migration. PI3K is regulated by the phosphatases PTEN (phosphatase and tensin homolog deleted on chromosome ten) and SHIP (SH2 domain-containing inositol 5-phosphatase). PTEN is a known tumor suppressor and mutated in human cancer with a frequency approaching that of p53. Surprisingly, while conditional deletion in T-cells (tPTEN) results in T-cell lymphoma, deletion in B-cells (bPTEN) does not result in transformation. In this proposal, the role of PTEN and SHIP in counter-acting PI3K activity and transformation-, in B-cells-, will be addressed through the use of double conditional knock-out mice and patient specimen analysis. In addition, the signal transduction pathways involved in transformation will be characterized and findings applied to the development of potential therapeutics for lymphoma. Finally, as preliminary cDNA array analysis reveals an inverse relationship between PTEN/SHIP expression and the severity of disease, (DLBCL

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01CA122192-04
Application #
7922520
Study Section
Subcommittee G - Education (NCI)
Program Officer
Lohrey, Nancy
Project Start
2007-09-30
Project End
2012-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
4
Fiscal Year
2010
Total Cost
$113,196
Indirect Cost
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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