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Sequence-specific enhancer binding protein is responsible for the differential expression of ERT/ESX/ELF-3/ESE-1/jen gene in human gastric cancer cell lines: Implication for the loss of TGF-β type II receptor expression

Oncogene volume 20, pages 1235–1245 (2001)Cite this article

Abstract

Transcriptional repression of the TGF-β type II receptor (RII) is one of the mechanisms leading to TGF-β resistance. The newly identified epithelium-specific ets transcription factor ERT/ESX/ELF-3/ESE-1/jen binds to the TGF-β RII promoter and induces promoter activity. The human gastric cancer cell lines, which show undetectable level of TGF-β RII mRNA, do not express ERT mRNA. To study the molecular mechanisms of loss of ERT expression, we have cloned and characterized the human ERT promoter. DNA transfection experiments and electrophoretic mobility shift assays have revealed the existence of a distinct enhancer element (−186 to −177) which we named ESE (ERT promoter specific element). Deletion of the ESE markedly decreased expression of the target gene. ESE interacts with two distinct nuclear protein complexes, at least one of which appears to be inactivated in a cell line which does not express the ERT mRNA, compared to a cell line expressing the ERT mRNA. These results suggest the possibility that inactivation of the sequence-specific DNA binding protein to the region from −186 to −177 contributes to the loss of ERT expression, leading to the loss of TGF-β type II receptor mRNA in human gastric cancer cell lines.

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Abbreviations

TGF-β:

transforming growth factor-β

TGF-β RII:

TGF-β type II receptor

EMSA:

eletrophoretic mobility shift assay

PCR:

polymerase chain reaction

RACE:

rapid amplification of cDNA end

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Acknowledgements

We thank Dr AB Roberts for helpful discussion and critical review of the manuscript.

Author information

Author notes

  1. Yong Seok Kim

    Present address: Department of Biochemistry, College of Medicine, Hanyang University, Seoul, Korea

  2. Susanne Hougaard

    Present address: University Hospital of Copenhagen, Denmark

Authors and Affiliations

  1. Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, 20892-5055, Maryland, MD, USA

    Seok Hee Park, Yong Seok Kim, Susanne Hougaard & Seong-Jin Kim

  2. Department of Pediatrics, Gyeongsang National University College of Medicine, Chinju, 660-702, Korea

    Byung-Kiu Park

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Park, S., Kim, Y., Park, BK. et al. Sequence-specific enhancer binding protein is responsible for the differential expression of ERT/ESX/ELF-3/ESE-1/jen gene in human gastric cancer cell lines: Implication for the loss of TGF-β type II receptor expression. Oncogene 20, 1235–1245 (2001). https://doi.org/10.1038/sj.onc.1204227

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