The basic helix-loop-helix transcription factor DEC2 inhibits TGF-β-induced             tumor progression in human pancreatic cancer BxPC-3 cells.
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.
Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan. fsatodec1dec2@yahoo.co.jp
Fuyuki
F
Sato
Haruka
H
Kawamura
Yunyan
Y
Wu
Hiroyasu
H
Sato
Daiki
D
Jin
Ujjal Kumar
UK
Bhawal
Takeshi
T
Kawamoto
Katsumi
K
Fujimoto
Mitsuhide
M
Noshiro
Hiroko
H
Seino
Satomo
S
Morohashi
Yukio
Y
Kato
Hiroshi
H
Kijima
D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D051792:Basic Helix-Loop-Helix Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C422085:BHLHE41 protein, human; C000604407:SNAI1 protein, human