Novel Role of ANX7 in Breast Cancer Progression
Abstract
The ANX7 gene codes for a Ca(2+) -activated GTPase, and is a tumor suppressor gene ANX7 expression has prognostic value for predicting survival of breast cancer patients. Our objective in this proposal is to determine the mechanism and the signaling pathway by which the ANX7 gene induces death of breast cancer cells. To this end, we have generated and identified the dominant negative mutants against calcium and GTP in the anx7 coding domain which are necessary for biochemical functions of ANX7. We also have generated the effective adenoviral constructs containing the dominant negative mutants and wt-ANX7 and have shown that altered ANX7 expression during breast cancer cell growth involves calcium. Additionally, we confirmed the role of calcium by determining ANX7's control on all three subtypes' of 11)3 Receptor expression. Using eDNA microarray and Western blot analysis, we have identified the downstream targets and signaling pathway, of ANX7 in apoptosis and suppression of breast cancer cell growth. Taken together, these data indicate that ANX7 suppresses breast cancer cell growth and calcium plays a role via 11)3-Receptor. In addition, we have identified the members of the ANX7 signaling pathway. Comprehensive effort is underway to validate the results that will further elucidate the ANX7 dependent calcium signaling pathway in breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA423765
Entities
People
- Meera Srivastava
Organizations
- Henry M. Jackson Foundation for the Advancement of Military Medicine