Accession Number:

ADA433099

Title:

The Tetraspanin Metastasis Suppressor Gene, KAI1/CD82, and the Proto-Oncogene, Her-2/neu, as Molecular Determinants of Metastasis in Breast Cancer Patients

Descriptive Note:

Annual summary rept. 21 Jul 2003-20 Jul 2004

Corporate Author:

TEXAS UNIV AT DALLAS SOUTHWESTERN MEDICAL CENTER

Personal Author(s):

Report Date:

2004-08-01

Pagination or Media Count:

29.0

Abstract:

The purpose of this research is to demonstrate that gene amplification of HER-2neu is associated with loss of expression of the tetraspanin metastasis suppressor gene, KAI1CD82, in breast cancer cell lines and patients primary breast tumors. The scope is limited to breast cancer and mechanisms of metastasis. Results 1 We identified three cell lines with gene amplification of HER-2neu and negative KAI1CD82 expression to serve as model systems and corroborated these results in primary breast tumors. 2 We found that CO-029, a tetraspanin metastasis promoter gene, was up-regulated in HER-2neu lines. 3 We ectopically expressed HER-2neu in MCF-7 cells and demonstrated that over-expression of HER-2neu resulted in loss of expression of KAI1CD82, but increased expression of CO-029. 4 Finally, we knocked down expression of HER-2neu by RNAi and demonstrated that KAI1CD82 levels increased four-fold. Significance HER-2neu signaling regulates tetraspanin gene expression to promote metastatic potential. This novel mechanism may explain why women with gene amplification of HER-2neu in their breast tumors are at higher risk for metastasis and death. This is the first demonstration of a receptor tyrosine kinase RTX that regulates tetraspanin metastasis genes, and this may be the first example of a broader paradigm linking RTK oncogenes to metastasis genes.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE