Differentiation and antiproliferation effects of retinoic acid receptor β in hepatoma cells

Evidence indicates that the retinoic acid receptor β (RARβ) gene might be a tumor suppressor gene. Previously, we have shown that the expression of the RARβ gene was either inhibited or downregulated in tumorigenic hepatoma cell lines such as McA-RH8994. McA-RH8994 cells expressed RARα and γ and three types of retinoid X receptor (RXRα, β and γ), but not RARβ mRNA. To further analyze the molecular mechanisms which might account for RARβ gene inactivation, the rat RARβ gene promoter was cloned from McA-RH8994 cells and no mutation was detected. By transient transfection, McA-RH8994 cells contained the necessary factors to activate the RARβ gene. To study the possible roles of RARβ in hepatoma cells, the expression of the RARβ gene was restored in McA-RH8994 cells by stable transfection. A RARβ positive cell line named McA-RH8994β was characterized. The results demonstrated that expression of the RARβ gene resulted in increased sensitivity of the hepatoma cells to the antiproliferative effect of retinoic acid (RA). Furthermore, expression of RARβ resulted in a spontaneous differentiation of the hepatoma cells. These data indicate that RARβ plays important roles in differentiation and antiproliferation.