Novel Role of ANX7 of Candidate Tumor Suppressor ANX7 Gene in Prostate Cancer
Abstract
Current attempts to develop more effective therapies for prostate cancer have been focussed on the discovery of new tumor suppressor genes, in hopes of using them for gene therapy. We have recently found that the ANX7 gene, which we discovered and have continued to study in the context of Ca2+ and GTP mediated exocytosis for many years (Creutz et al, 1978; ibid, 1979; Raynal and Pollard, 1994; Caohuy et al, 1996; Srivastava et al, 1996), is defective in 35% of human prostate cancer specimens (Srivastava et al., 2001 a) and 40% of human breast cancer specimens. A detailed analysis of ANX7 levels in hundreds of prostate cancer specimens reveals that expression of this candidate tumor suppressor gene is specifically altered in metastatic and hormone refractory prostate cancers (Srivastava et al., 2001 a). These data therefore, strongly suggest that the ANX7 gene has clinical relevance for prostate cancer in men. This is an important insight because until now the ANX7 gene has never been thought to play such a role (Raynal and Pollard, 1994). In our preliminary studies with metastatic prostate cancer cells in vitro, we find that ANX7 gene therapy causes these cells to undergo apoptosis, or programmed cell death. Therefore our objective in this proposal is to determine the mechanism and the signaling pathway by which the ANX7 gene induces death of prostate cancer cells. The rationale behind this study is the hope that such knowledge will enable us to develop therapies based on the use of the ANX7 gene to treat or prevent prostate cancer. We are best positioned to pursue this work because we not only discovered the ANX7 gene, but have also recently prepared a tumor-prone Anx7 knockout mouse. It has fascinated us that the phenotype of this knockout mouse also includes such a high frequency (20-25%) of spontaneous tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2004
- Accession Number
- ADA427655
Entities
People
- Meera Srivastava
Organizations
- Henry M. Jackson Foundation for the Advancement of Military Medicine