Bin1, Apoptosis, and Prostate Cancer
Abstract
Progress is summarized on our project to investigate the diagnostic and therapeutic potential for Bin1 in prostate cancer. We have successfully generated 9 new monoclonal antibodies capable of recognizing all Bin1 splice isoforms that have been identified in cells. These antibodies are currently being tested and optimized for staining of fixed tissues. In Aim 2, we proposed to perform immunohistochemical studies. To date, we have analyzed 30 cases of frozen primary prostate cancer and found that 29/30 retained Bin1 expression in epithelial cells. Additional cases including metastatic cancers with follow-up information are pending completion of antibody testing. We believe this line of work will prove informative, because Northern analysis of primary and metastatic cancers confirms frequent expression in primaries but indicates universal losses in metastatic tumors. To date, gene status has been examined in 15 primary tumors. Using a heterozygous marker within the Bin1 gene we have documented loss of heterozygosity (LOH) in 6/15 of these tumors (40% LOH rate). However, the remaining alleles in tumors exhibiting LOH did not show alteration or perhaps only polymorphism rather than mutation. Metastatic variants of these tumors were not available to learn whether mutation had occurred later in progression. This possibility is viable insofar as we have observed expression of normal Bin1 message in androgen-dependent LNCaP cells but misplaced messages that encode inactive polypeptides in androgen-independent PC3 and DU145 cells. Further analysis of Bin1 in metastatic tumors is planned as is an examination of promoter methylation status. Functional investigations indicate that LNCaP and PC3 are relatively susceptible to growth inhibition by Bin1 whereas DU145 is relatively insensitive, Adenoviral vectors for Bin1 are nonspecifically toxic in our hands.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2002
- Accession Number
- ADA405309
Entities
People
- Frank K. Rauscher
Organizations
- Wistar Institute