S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
Truncation of the TGF-β type II receptor gene results in insensitivity to TGF-β in human gastric cancer cells
- Yang, Han-Kwang; Kang, Shin Hyeok; Kim, Yong-Seok; Won, Kyungshick; Bang, Yung-Jue; Kim, Seong-Jin
- Issue Date
- Oncogene, Vol.18 No.13, pp.2213-2219
- The transforming growth factor-beta (TGF-beta receptor system has been implicated in the development of resistance to the growth-inhibitory effects of TGF-beta. It has been reported that resistance to TGF-beta correlates with inactivation of the TGF-beta type II receptor (RII). In the present report, we examine the genetic changes in the TGF-beta RII gene of human gastric cancer cell lines, SNU-5 and SNU-668, which we had previously reported to express truncated TGF-beta RII transcripts. By independent PCR and Southern hybridization analysis of genomic DNA, we found that the genomic sequence of TGF-beta RII is truncated after exon 2 in SNU-5 and after exon 3 in SNU-668. This was confirmed by sequencing the TGF-beta RII cDNA cloned from a SNU-5 cDNA library. Predicted TGF-beta RII protein of SNU-5 cells based on sequencing data contains only a part of extracellular domain of TGF-beta RII. We demonstrate that cotransfection of 3TP-Lux and wild type TGF-beta RII restores the TGF-beta responsiveness in SNU-5 cells, suggesting that genetic changes in the TGF-beta RII gene of SNU-5 cells are responsible for the loss of sensitivity to TGF-beta. This is the first report demonstrating that truncation of the TGF-beta RII gene is an alternative mechanism to inactivate the TGF-beta signal transduction pathways.
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