Differentiation-inducing factor-1 suppresses gene expression of cyclin D1 in tumor cells

Tania Yasmin, Fumi Takahashi-Yanaga, Jun Mori, Yoshikazu Miwa, Masato Hirata, Yutaka Watanabe, Sachio Morimoto, Toshiyuki Sasaguri

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27 Citations (Scopus)


To determine the mechanism by which differentiation-inducing factor-1 (DIF-1), a morphogen of Dictyostelium discoideum, inhibits tumor cell proliferation, we examined the effect of DIF-1 on the gene expression of cyclin D1. DIF-1 strongly reduced the expression of cyclin D1 mRNA and correspondingly decreased the amount of β-catenin in HeLa cells and squamous cell carcinoma cells. DIF-1 activated glycogen synthase kinase-3β (GSK-3β) and inhibition of GSK-3β attenuated the DIF-1-induced β-catenin degradation, indicating the involvement of GSK-3β in this effect. Moreover, DIF-1 reduced the activities of T-cell factor (TCF)/lymphoid enhancer factor (LEF) reporter plasmid and a reporter gene driven by the human cyclin D1 promoter. Eliminating the TCF/LEF consensus site from the cyclin D1 promoter diminished the effect of DIF-1. These results suggest that DIF-1 inhibits Wnt/β-catenin signaling, resulting in the suppression of cyclin D1 promoter activity.

Original languageEnglish
Pages (from-to)903-909
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - Dec 16 2005

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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