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

✍ Scribed by Kuniko Horie; Hidetoshi Yamashita; Akira Mogi; Seiichi Takenoshita; Kohei Miyazono

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 319 KB
• Volume: 175
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/(sici)1097-4652(199806)175:3<305::aid-jcp8>3.0.co;2-s

✦ Synopsis

Retinoblastoma cells are resistant to transforming growth factor-b (TGF-b) activity due to the absence of TGF-b binding. To further elucidate the mechanism of TGF-b resistance, we studied the expression of the TGF-b receptors and SMADs by using the Y79 and WERI-Rb-1 retinoblastoma cell lines. Binding of 125 I-TGF-b1 to serine/threonine kinase receptor type II (TbR-II) and TbR-I was not seen in the retinoblastoma cells. TbR-II mRNA was not expressed in these cells, but TbR-I mRNA was detected. Mutation analysis revealed no mutation in the coding region of the TbR-II gene, and TbR-II mRNA could be induced after the differentiation of Y79 cells. Smad2, Smad3, and Smad4, which are involved in TGF-b signaling, were expressed in the retinoblastoma cells. Transcriptional activation of the TGF-b-responsive genes was not seen by the transfection of either receptor cDNA alone but could be induced by transfection of both TbR-II and TbR-I. These data suggest that the defect in the TGF-b response is caused by the lack of TbR-II in the retinoblastoma cells. In addition, TbR-I may be functionally inactivated in these cell lines.