The basic helix-loop-helix transcription factor DEC2 inhibits TGF-β-induced tumor progression in human pancreatic cancer BxPC-3 cells

Sato,Fuyuki; Kawamura,Haruka; Wu,Yunyan; Sato,Hiroyasu; Jin,Daiki; Bhawal,Ujjal Kumar; Kawamoto,Takeshi; Fujimoto,Katsumi; Noshiro,Mitsuhide; Seino,Hiroko; Morohashi,Satomo; Kato,Yukio; Kijima,Hiroshi

doi:10.3892/ijmm.2012.1037

The basic helix-loop-helix transcription factor DEC2 inhibits TGF-β-induced tumor progression in human pancreatic cancer BxPC-3 cells

Authors:
- Fuyuki Sato
- Haruka Kawamura
- Yunyan Wu
- Hiroyasu Sato
- Daiki Jin
- Ujjal Kumar Bhawal
- Takeshi Kawamoto
- Katsumi Fujimoto
- Mitsuhide Noshiro
- Hiroko Seino
- Satomo Morohashi
- Yukio Kato
- Hiroshi Kijima
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Affiliations: Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan, Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry, Matsudo, Chiba 271-8587, Japan, Department of Dental and Medical Biochemistry, Hiroshima University Graduate School of Biomedical Science, Hiroshima 734-8553, Japan
Published online on: June 19, 2012 https://doi.org/10.3892/ijmm.2012.1037
Pages: 495-501

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Abstract

The basic helix loop helix (bHLH) transcription factor DEC2 is associated with the regulation of apoptosis, circadian rhythm and the response to hypoxia. However, the significance of DEC2 in pancreatic cancer remains unknown. Here, we showed for the first time that DEC2 inhibits the progression of human pancreatic cancer. Human pancreatic cancer BxPC-3 cells were treated with or without transforming growth factor-β (TGF-β), siRNA against DEC2, or a combination of TGF-β and DEC2 siRNA or DEC2 overexpression. The cells were analyzed by RT-PCR, real-time PCR, western blotting, immunofluorescent staining and ChIP assay. We also performed immunohistochemical analyses of DEC2 expression in surgically-resected pancreatic cancers. The expression of DEC2 was increased in TGF-β-treated BxPC-3 cells. In the presence of TGF-β, DEC2 overexpression decreased the migration and invasion of BxPC-3 cells. Knockdown of DEC2 by siRNA in the presence of TGF-β significantly increased the expression and nuclear concentration of slug. We also showed that DEC2 siRNA decreased the binding of DEC2 to the E-box of the slug promoter. Immunohistochemically, little DEC2 was detected in pancreatic cancer tissues, whereas significant amounts were detected in the adjacent non-cancerous pancreatic tissues. These results indicate that DEC2 has inhibitory effects against human pancreatic cancer that involve TGF-β and slug.

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