Lack of transforming growth factor-beta type II receptor expression in human retinoblastoma cells

Abstract

Retinoblastoma cells are resistant to transforming growth factor-beta (TGF-beta) activity due to the absence of TGF-beta binding. To further elucidate the mechanism of TGF-beta resistance, we studied the expression of the TGF-beta receptors and SMADs by using the Y79 and WERI-Rb-1 retinoblastoma cell lines. Binding of 125I-TGF-beta1 to serine/threonine kinase receptor type II (TbetaR-II) and TbetaR-I was not seen in the retinoblastoma cells. TbetaR-II mRNA was not expressed in these cells, but TbetaR-I mRNA was detected. Mutation analysis revealed no mutation in the coding region of the TbetaR-II gene, and TbetaR-II mRNA could be induced after the differentiation of Y79 cells. Smad2, Smad3, and Smad4, which are involved in TGF-beta signaling, were expressed in the retinoblastoma cells. Transcriptional activation of the TGF-beta-responsive genes was not seen by the transfection of either receptor cDNA alone but could be induced by transfection of both TbetaR-II and TbetaR-I. These data suggest that the defect in the TGF-beta response is caused by the lack of TbetaR-II in the retinoblastoma cells. In addition, TbetaR-I may be functionally inactivated in these cell lines.