Michelle A. Rider, M.S.

Thesis research performed under the guidence of Dr. William B. Coleman

ABSTRACT
    Aberrations of human chromosome 13 have been documented in hepatocellular carcinomas, suggesting that liver tumor suppressor genes may be located on this chromosome.  Microcell-mediated introduction of human chromosome 13 into the rat liver tumor cell line GN6TF resulted in the generation of clonal microcell hybrid cell lines that differentially exhibited tumor suppression and alteration of other transformation-associated phenotypes in vitro.  Suppressed lines demonstrated a reversion to a normalized morphology, while non-suppressed cell lines were nearly indistinguishable from the parental GN6TF tumor cells.  Tumors derived from non-suppressed lines expressed mRNA for Rb1 and BRCA2, and expressed the pRb1 protein, suggesting that the molecular mechanism governing tumorigenisis in the cells was refractory to suppression by pRb.  These studies describe characterization of a model system useful in the study of liver tumor suppression mediated by chromosome 13, for examination of the role of known tumor suppressor genes and identification of novel loci.