Pancreatic adenocarcinoma is the fifth leading cause of adult cancer mortality in the United States, and treatments for this cancer are largely ineffective. However, a better understanding of the molecular basis of pancreatic tumorigenesis may aid in the design of more effective therapeutic strategies. They plan to improve this understanding by studying Rel/NF-kB. This family of transcription factors is involved in the differentiation of immune cells and organs, tumorigenic transformation, embryonic development, and apoptosis. In previous studies, they detected constitutively active Rel/NFkB in 14 of 20 (70 percent) pancreatic adenocarcinomas but not in normal pancreas. They also detected it in 7 of 11 (64 percent) human pancreatic tumor cell lines. The activated Rel/NFkB may inhibit apoptotic stimuli through induction of bcl-2 gene expression. So, they hypothesize that (1) constitutively activated RelA plays a critical role in pancreatic tumorigenesis and/or inhibits pro-apoptotic stimulation by inducing the expression of downstream target genes and (2) inhibition of RelA plays a critical role in pancreatic tumorigenesis and/or inhibits pro-apoptotic stimulation by inducing the expression of downstream target genes and (2) inhibition of RelA activity may repress tumor formation and/or render these tumor cells more susceptible to apoptosis induced by anticancer drugs. To test the hypothesis, they will specific inhibit or activate Rel/NFkB to determine the significance of this alteration for growth and apoptosis, to determine if bcl-2 is the downstream target gene regulated by Rel/NFkB, and to determine if MAP kinases constitute the upstream signal transduction pathway for Rel/NFkB activation. The studies may lead to the development of specific inhibitors of Rel/NFkB for use in novel therapies for pancreatic cancers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA073675-03
Application #
6124539
Study Section
Pathology B Study Section (PTHB)
Program Officer
Spalholz, Barbara A
Project Start
1998-01-09
Project End
2002-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
3
Fiscal Year
2000
Total Cost
$104,202
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Internal Medicine/Medicine
Type
Other Domestic Higher Education
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
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