The applicant has identified the beta6 subunit, showed it forms heterodimers with alphav, and functions as a fibronectin receptor. Moreover, its expression is limited to epithelia and increases dramatically during development, wound healing, inflammation, and during malignant transformation. The largest expression of alphavbeta6 is found at invasive edges of carcinomas, and the applicant has found that transfection of beta6 in to colon cancer cells increases their proliferation in a collagen gel. Based on these data, he hypothesizes that alphavbeta6 plays a critical role in the invasive growth of carcinomas cells in vivo. To test this hypothesis, he will examine the migration of carcinoma cells out of freshly explanted tumors into a three dimensional collagen-fibronectin matrix. He will examine the distribution of alphavbeta6 under these conditions, and determine whether antibodies to alphavbeta6 interfere with migration. He will then characterize a series of mouse lines expressing oncogenes such as c-neu, c-src, and polyoma middle T under control of mouse mammary tumor virus promoter. The distribution of alphavbeta6 in tumor tissue of these mice will be analyzed and correlated with tumor progression in oncogene expression. Finally, these mice that develop beta6 positive tumors will be crossed with beta6 null mice, to determine whether some difference in tumor cell behavior is observed.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA053250-07
Application #
2633819
Study Section
Pathobiochemistry Study Section (PBC)
Program Officer
Mohla, Suresh
Project Start
1991-01-01
Project End
1999-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
7
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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