Meeting Abstract

P2.104  Wednesday, Jan. 5  Validating a potential pre-clinical cancer model: Inactivation of the tumor suppressor p53 in colon carcinoma cell lines. GESTL, E.G.; TARASKA, N.G.; TERKOWSKI, S.M.; GIOVENELLA, R.C; BOETTGER, S.A.*; West Chester University of Pennsylvania; West Chester University of Pennsylvania; West Chester University of Pennsylvania; West Chester University of Pennsylvania; West Chester University of Pennsylvania aboettger@wcupa.edu

Cancers are a vital threat to human health and it is important to identify pre-clinical animal models are not highly regulated, inexpensive to maintain, occur naturally and may be used for in vitro and in vivo studies simultaneously. Hemic neoplasia (a blood cancer or leukemia) found in bivalve mollusks offers significant advantages over traditional models for preclinical analysis of treatments for human cancers with a similar molecular basis. This naturally occurring model resembles an outbreeding, human clinical population compared to those generated from inbred mouse strains or by intentional exposure to known tumor viruses. It is the best characterized, naturally occurring malignancy with known molecular mechanisms similar to those observed in unrelated human colorectal carcinomas where a tumor suppressor protein (p53) is inactivated by binding to another protein, mortalin. Human colorectal carcinomas were examined for similarities to clam cancer regarding mechanisms of inactivation, the cytoplasmic sequestration of the tumor suppressor gene p53 in the cell cytoplasm by the heat shock protein family member mortalin and overexpression of mortalin. This first step in validating the clam cancer model as a screening tool for potential human anti-tumor agents will generate a model for preclinical analysis more similar to an outbreeding human population than expensive and difficult to maintain inbred vertebrate models currently used (Supported by ENDO Pharmaceuticals funds to SAB and EEG)