Anchorage-independent growth is a hallmark of colon cancer cells in general. Growth factors and the extracellular matrix coordinated stimulate normal cell proliferation. This is mediated principally by growth factor receptors and integrin receptors whose signaling pathways converge at several levels within cells. Autocrine growth factor - EGFR loops are vital to the proliferation of many colon cancer cell lines. During colonic tumorigenesis, integrin expression is greatly diminished, and the specific loss of alpha 5/beta I integrin heterodimer expression has been observed in vivo. Transfection of alpha 5 integrin into malignant CHO cells devoid of alpha 5/beta I integrin expression abrogates the malignant phenotype and inhibits their proliferation. Thus, we hypothesize that transfection of alpha 5 integrin into colon cancer cell lines lacking alpha 5 integrin expression will decrease their growth by directly inhibiting the EGFR signal transduction pathway. The primary aims of this proposal are to demonstrate that alpha 5 integrin expression in colon cancer cells: reverses anchorage- independent growth; inhibits their proliferation by compartmentalizing, deactivating (decreased phosphorylation), or decreasing protein expression of EGFR signal transduction pathway kinases. The demonstration of a direct modulation of EGFR- mediated cell growth by a single integrin would expand our knowledge of how colon cancer cells escape anchorage-dependent growth control, and might lead to novel therapeutic strategies for colon cancer based on growth regulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DK002531-02
Application #
2733841
Study Section
Special Emphasis Panel (SRC)
Program Officer
Podskalny, Judith M,
Project Start
1997-07-10
Project End
2002-06-30
Budget Start
1998-09-30
Budget End
1999-06-30
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Utah
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112