Apoptosis and Tumor Progression in Prostate Cancer
Abstract
In the period covered by this application, we have established that the PC-346CRFP can be used as a suitable model for androgen dependent localized prostate cancer. We have shown that orthotopic tumors derived from PC-346CRFP cells (inoculated in growth factor replete Matrigel into the ventral prostate of nude mice) are responsive to Asodex, and undergo tumor regression as a consequence of an increase in apoptosis and a decrease in proliferation rate. LNCap cells selected on the basis of their invasive potential in vitro however do not respond to Casodex and do not metastasize to other organs. We attribute this to the presence of a mutated Androgen receptor in the LNCaP cells which responds to the adrenal steroid dehydroepiandrosterone (DHEA), overriding the effects of Casodex, and to the high levels of growth factors. When inoculated in growth factor depleted Matrigel PC-346CRFP cells form primary tumors, and after extended treatment with Casodex, show evidence of metastatic progression after treatment with Casodex, although the data has not yet reached statistical relevance. Micro-array and macro-array techniques are being used to characterize the expression of genes induced by Casodex in this tumor to identify the genes that may underlie tumor progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2004
- Accession Number
- ADA423481
Entities
People
- Martin P. Tenniswood
Organizations
- University of Notre Dame