摘要

Evidence indicates that the retinoic acid receptor beta (RAR beta) gene might be a tumor suppressor gene. Previously, we have shown that the expression of the RAR beta gene was either inhibited or downregulated in tumorigenic hepatoma cell lines such as McA-RH8994. McA-RH8994 cells expressed RAR alpha and gamma and three types of retinoid X receptor (RXR alpha, beta and gamma), but not RAR beta mRNA. To further analyze the molecular mechanisms which might account for RAR beta gene inactivation, the rat RAR beta 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 RAR beta gene. To study the possible roles of RAR beta in hepatoma cells, the expression of the RAR beta gene was restored in McA-RH8994 cells by stable transfection. A RAR beta positive cell line named McA-RH8994 beta was characterized. The results demonstrated that expression of the RAR beta gene resulted in increased sensitivity of the hepatoma cells to the antiproliferative effect of retinoic acid (RA). Furthermore, expression of RAR beta resulted in a spontaneous differentiation of the hepatoma cells. These data indicate that RAR beta plays important roles in differentiation and antiproliferation.

  • 出版日期1998-2-27
  • 单位UCLA