RB1 ONCOSUPPRESSOR GENE OVER-EXPRESSION INHIBITS TUMOR PROGRESSION AND INDUCES MELANOGENESIS IN METASTATIC MELANOMA-CELLS

The retinoblastoma gene (RB1) is frequently deleted or mutated in many tumor types and in all cases of retinoblastoma. Apart from its role i n regulation of the cell cycle, the RB1 gene product (p110(RB1)) appea rs to be involved in control of differentiation, Malignant metastatic cells show many properties of poorly differentiated cells, and are hig hly invasive in vitro and in vivo. We have transfected the human RB1 c DNA in an expression vector under the control of the beta-actin promot er into B16F10 murine melanoma cells. These cells highly overexpress R B1 mRNA and the p110(RB1) product, show reduced growth rate and increa sed melanogenesis in vitro. Vector control transfectants showed no alt eration of invasiveness. The p110(RB1) over-expressing cells also had a reduced capacity to migrate and invade through an artificial basemen t membrane, key characteristics of metastatic cells. When injected int o nude mice, the p110(RB1) over-expressing cells showed reduced tumor growth and reduced metastatic potential, The few metastasis observed w ere predominantly melanotic. These data indicate that RB1 gene express ion is involved in melanoma cell differentiation and plays a role in d ownregulation of migration, invasion and metastatic potential of these cells.