Transforming growth factor (TGF-beta) is a multi-functional factor that induces a wide variety of cellular processes affecting growth and differentiation. In normal epithelial cells, including intestinal epithelium, TGF-beta has a potent growth inhibitory effect and serves a tumor suppressor role. On the other hand, under selected conditions TGF-beta may actually promote tumorigenesis. Mutations in the TGF-beta receptors and selected TGF-beta signal transduction proteins (Smad family of proteins) have been associated with a significant fraction of human colorectal and pancreatic cancers. Evidence suggests that several effects of TGF-beta such as increased chemotactic activity and invasiveness, increased expression of COX-2 and prostaglandin release and increased expression of RhoB cause a epithelial to mesenchymal expression of COX-2 and prostaglandin release and increased expression of RhoB cause a epithelial to mesenchymal transition (EMT). Based on recent observations, the central hypothesis of this proposal is: tumor promoting effects of TGF-beta over-ride tumor suppressor effects during of intestinal and other types of epithelial cells, due to a witch in TGF-beta signal transduction. A long term of this investigation is to identify novel therapeutic strategies that selectively target the tumor promoting effects of TGF-beta, while preserving the tumor suppressive actions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DK010138-01
Application #
6210159
Study Section
Special Emphasis Panel (ZRG1-SSS-3 (02))
Program Officer
Podskalny, Judith M,
Project Start
2000-11-01
Project End
Budget Start
2000-11-01
Budget End
2001-10-31
Support Year
1
Fiscal Year
2000
Total Cost
$39,232
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Surgery
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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