Lymphoid enhancer factor 1 makes cells resistant to transforming growth factor β-induced repression of c-myc

Toru Sasaki, Hiroyuki Suzuki, Ken Yagi, Masao Furuhashi, Ryoji Yao, Shinji Susa, Tetsuo Noda, Yoichi Arai, Kohei Miyazono, Mitsuyasu Kato

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Abstract

The activation of lymphoid enhancer factor (LEF)/T-cell factor (TCF)-mediated transcription by sustained expression of β-catenin and the loss of transforming growth factor β (TGF-β) signaling are essential steps in carcinogenesis, particularly for cancers of the colon, breast, and liver. The oncogene c-myc is a common target of both of these signaling pathways and a key regulator of cell cycle progression. Here we have identified a novel LEF/TCF-responsive element in the promoter of the human c-myc gene. β-Catenin activated the transcriptional activity of the c-myc promoter by binding to this element in various cell lines. When TCF-4 was bound to this element, TGF-β dissociated β-catenin and repressed the transcriptional activity of the c-myc promoter. However, TGF-β could not dissociate β-catenin and could not repress c-myc transcription when LEF-1 was bound to the element instead of TCF-4. These findings suggest that enhanced expression of LEF-1, which occurs frequently in colon cancer, may make cells refractory to the down-regulation of c-myc and the subsequent growth arrest induced by TGF-β.

Original languageEnglish
Pages (from-to)801-806
Number of pages6
JournalCancer Research
Volume63
Issue number4
Publication statusPublished - 2003 Feb 15

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Sasaki, T., Suzuki, H., Yagi, K., Furuhashi, M., Yao, R., Susa, S., Noda, T., Arai, Y., Miyazono, K., & Kato, M. (2003). Lymphoid enhancer factor 1 makes cells resistant to transforming growth factor β-induced repression of c-myc. Cancer Research, 63(4), 801-806.