Jennifer E. Jahn, Ph.D.

Dissertation research performed under the direction of William B. Coleman

ABSTRACT
    The molecular pathogenesis of hepatocellular carcinoma is well-studied but not completely understood. We utilized a microcell-hybrid model approach to facilitate the identification of novel liver tumor suppressor genes located on human chromosome 11. These investigations confirmed a liver tumor suppressor locus at human chromosome 11p11.2, and subsequently identified SYT13 as the gene responsible for the suppression of tumorigenicity in rat liver tumor cell lines. Complementary approaches involving both silencing SYT13 in suppressed microcell-hybrid cell lines and expressing SYT13 in tumor cell lines showed that this gene is both required and sufficient for 11p11.2-mediated suppression of tumorigenicity in the GN6TF rat liver tumor cell line. Furthermore, the results strongly suggest that the dimerized form of the SYT13 protein is necessary for tumor suppressor function and that tumor suppression may be affected through pathways implicated in epithelial to mesenchymal transition. These observations also suggest that the deficit in GN6TF that leads to the tumorigenic phenotype involves loss of the ability of the endogenous Syt13 to dimerize, perhaps through protein misfolding or loss of post-translational processing.