PROMOTER-INDEPENDENT LOSS OF MESSENGER-RNA AND PROTEIN OF THE RB GENEIN A HUMAN HEPATOCELLULAR-CARCINOMA

Background: Inactivation of the retinoblastoma (Rb) gene is considered to play a fundamental role in the genesis and progression of several human cancers. In retinoblastoma, the inactivation of Rb promoter by m utations or hypermethylation has been reported. Although genetic chang es of Rb gene have been described in hepatocellular carcinoma (HCC) an , epigenetic change such as hypermethylation of the Rb promoter as rep orted in, retinoblastoma has not been described.Materials and Methods: We examined the hypermethylation in the promoter region of Rb gene by restriction fragment length polymorphism in 19 HCCs, as well as the e xpression of Rb mRNA and protein by RT-PCR and by immunoblotting, resp ectively. Results: We found no evidence of hypermethylation. in the pr omoter region, of the Rb gene in all HCCs analyzed. However, the expre ssion of Rb mRNA and protein was lost in one HCC, and no mutation was detected in the Rb promoter region of this patient. The inactivation o f Rb promoter by hypermethylation or by inhibition of binding of trans cription factors due to point mutations did not contribute to the loss of mRNA and protein in. the patient. Conclusions: Hypermethylation in the Rb promoter region appeared to have little causal effect on HCC.