LACK OF TRANSFORMING-GROWTH-FACTOR-BETA TYPE-II RECEPTOR EXPRESSION IN HUMAN RETINOBLASTOMA CELLS

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 expres sion of the TGF-beta receptors and SMADs by using the Y79 and WERI-Rb- 1 retinoblastoma cell lines. Binding of I-125-TGF-beta 1 to serine/thr eonine kinase receptor type II (T beta R-II) and T beta R-I was not se en in the retinoblastoma cells. T beta R-II mRNA was not expressed in these cells, but T beta R-I mRNA was detected. Mutation analysis revea led no mutation in the coding region of the T beta R-II gene, and T be ta R-II mRNA could be induced after the differentia tion of Y79 cells. Smad2, Smad3, and Smad4, which are involved in TGF-P signaling, were expressed in the retinoblastoma cells. Transcriptional activation of t he TGF-beta-responsive genes was not seen by the transfection of eithe r receptor cDNA alone but could be induced by transfection of both T b eta R-II and T beta RI. These data suggest that the defect in the TGF- beta response is caused by the lack of T beta R-II in the retinoblasto ma cells. In addition, T beta R-I may be functionally inactivated in t hese cell lines. (C) 1998 Wiley-Liss, Inc.