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Truncation of the TGF-β type II receptor gene results in insensitivity to TGF-β in human gastric cancer cells

Abstract

The transforming growth factor-β (TGF-β receptor system has been implicated in the development of resistance to the growth-inhibitory effects of TGF-β. It has been reported that resistance to TGF-β correlates with inactivation of the TGF-β type II receptor (RII). In the present report, we examine the genetic changes in the TGF-β RII gene of human gastric cancer cell lines, SNU-5 and SNU-668, which we had previously reported to express truncated TGF-β RII transcripts. By independent PCR and Southern hybridization analysis of genomic DNA, we found that the genomic sequence of TGF-β RII is truncated after exon 2 in SNU-5 and after exon 3 in SNU-668. This was confirmed by sequencing the TGF-β RII cDNA cloned from a SNU-5 cDNA library. Predicted TGF-β RII protein of SNU-5 cells based on sequencing data contains only a part of extracellular domain of TGF-β RII. We demonstrate that cotransfection of 3TP-Lux and wild type TGF-β RII restores the TGF-β responsiveness in SNU-5 cells, suggesting that genetic changes in the TGF-β RII gene of SNU-5 cells are responsible for the loss of sensitivity to TGF-β. This is the first report demonstrating that truncation of the TGF-β RII gene is an alternative mechanism to inactivate the TGF-β signal transduction pathways.

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Abbreviations

TGF-β:

transforming growth factor β

RI:

receptor type I

RII:

receptor type II

WT:

wild type

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Acknowledgements

We thank Dr Anita Roberts for helpful discussion and critical review of the manuscript. This study was in part supported by the KOSEF through the CRC at Seoul National University, Korea.

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Yang, HK., Kang, S., Kim, YS. et al. Truncation of the TGF-β type II receptor gene results in insensitivity to TGF-β in human gastric cancer cells. Oncogene 18, 2213–2219 (1999). https://doi.org/10.1038/sj.onc.1202535

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