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Accession Number:
ADB274286
Title:
Characterization of an Adhesion-Associated Tumor Suppressor in Breast Cancer
Corporate Author:
PURDUE RESEARCH FOUNDATION LAFAYETTE IN
Report Date:
2001-08-01
Abstract:
The DV antigen was identified in a screen of monoclonal antibodies that recognized tyrosine kinases and their substrates in breast cancer cells. DV was found to be differentially expressed in normal, non-malignant and malignant breast epithelial cells. In our funded proposal, we identified DV as the EphA2 receptor tyrosine kinase. We also found that EphA2 function is regulated by the E-cadherin tumor suppressor protein. Specifically, E-cadherin causes EphA2 to negatively regulate breast cancer cell growth and invasiveness. However, in the most aggressive breast cancers, E-cadherin function is frequently lost. Consequently, the EphA2 in metastatic cells is overexpressed and functionally altered and these changes cause EphA2 to promote metastatic cell growth. These defects in EphA2 could be overcome using monoclonal antibodies or fusion proteins and this facilitated selective inhibition of the growth and invasiveness of metastatic breast cancer cells. The information learned in our studies has identified a key regulator of breast cancer cell growth and invasiveness. Moreover, our studies indicate that EphA2 holds potential as a target for therapeutic intervention against metastatic breast cancer.
Descriptive Note:
Final rept. 1 Aug 1998-31 Jul 2001
Pages:
0051
Contract Number:
DAMD17-98-1-8146
File Size:
4.32MB
