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 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.
Horie
K
K
Department of Biochemistry, The Cancer Institute, Tokyo, Japanese Foundation for Cancer Research, Japan.
Yamashita
H
H
Mogi
A
A
Takenoshita
S
S
Miyazono
K
K
D030201:Activin Receptors, Type I; D000818:Animals; D002460:Cell Line; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008907:Mink; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D012175:Retinoblastoma / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics; D015533:Transcriptional Activation / Q000502:physiology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II