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

J Cell Physiol. 1998 Jun;175(3):305-13. doi: 10.1002/(SICI)1097-4652(199806)175:3<305::AID-JCP8>3.0.CO;2-S.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type I*
  • Animals
  • Cell Line
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mink
  • Mutation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics*
  • Receptors, Transforming Growth Factor beta / metabolism
  • Retinoblastoma / genetics*
  • Retinoblastoma / metabolism
  • Signal Transduction / physiology
  • Smad2 Protein
  • Smad3 Protein
  • Smad4 Protein
  • Trans-Activators / genetics
  • Transcriptional Activation / physiology
  • Transfection
  • Transforming Growth Factor beta / metabolism
  • Tumor Cells, Cultured

Substances

  • DNA-Binding Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Transforming Growth Factor beta
  • SMAD2 protein, human
  • SMAD3 protein, human
  • SMAD4 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • Smad4 Protein
  • Trans-Activators
  • Transforming Growth Factor beta
  • Protein-Serine-Threonine Kinases
  • Activin Receptors, Type I
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II