Differentiation-inducing factor-1 suppresses gene expression of cyclin D1 in tumor cells
- Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan)
- Department of Molecular and Cellular Biochemistry, Graduate School of Dental Sciences, Kyushu University, Fukuoka 812-8582 (Japan)
- Department of Applied Chemistry, Faculty of Engineering, Ehime University, Matsuyama 790-8577 (Japan)
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 {beta}-catenin in HeLa cells and squamous cell carcinoma cells. DIF-1 activated glycogen synthase kinase-3{beta} (GSK-3{beta}) and inhibition of GSK-3{beta} attenuated the DIF-1-induced {beta}-catenin degradation, indicating the involvement of GSK-3{beta} 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/{beta}-catenin signaling, resulting in the suppression of cyclin D1 promoter activity.
- OSTI ID:
- 20793218
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 338, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2005.10.018; PII: S0006-291X(05)02264-3; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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