The long-term objective of this project is to understand how cell-cell interactions are down-regulated in invasive carcinomas. The hypothesis to be tested is that a novel mechanism of E-cadherin inactivation occurs in some tumors, thus promoting loss of cell-cell interactions. It is proposed that expression of an inappropriate cadherin (i.e., a mesenchymal cadherin in an epithelial cell) down-regulates the normal endogenous epithelial cadherin(s). Preliminary data have been obtained suggesting that inappropriate expression of N-cadherin by squamous epithelial cells both down-regulates E-cadherin and results in decreased cell-cell adhesion and a more scattered, fibroblast-like morphology.
The specific aims are: 1) To determine which domain(s) of N-cadherin are responsible for down-regulating the expression of E-cadherin and for producing a fibroblastic phenotype in oral squamous epithelial cells; 2) To determine whether N-cadherin is unique in its ability to alter the phenotype of squamous epithelial cells by determining if other non-epithelial cell cadherins (e.g., cadherin 4, cadherin 6 or cadherin 11) produce similar results; and 3) To determine the mechanisms that confer a scattered phenotype upon squamous epithelial cells. The change in phenotype may be due to a number of activities including decreased cell-cell adhesion or increased motility. To help sort out these two possibilities, studies will be performed to down-regulate E-cadherin expression without the complications of altering the expression of N-cadherin.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
3R01DE012308-06S1
Application #
6553270
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Shirazi, Yasaman
Project Start
1998-04-01
Project End
2003-01-31
Budget Start
2002-02-01
Budget End
2003-01-31
Support Year
6
Fiscal Year
2002
Total Cost
$41,660
Indirect Cost
Name
University of Nebraska Medical Center
Department
Dentistry
Type
Schools of Dentistry
DUNS #
City
Omaha
State
NE
Country
United States
Zip Code
68198
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