title: Basic helix-loop-helix transcription factor DEC1 negatively regulates cyclin D1.
abstract: DEC1 (also known as Stra13/Bhlhb2/Sharp2) and DEC2 (also known as Bhlhb3/Sharp1) are two paralogous basic helix-loop-helix (bHLH) transcriptional regulators which exhibit a robust circadian gene expression pattern in the suprachiasmatic nucleus (SCN) and in peripheral organs. DEC1 has been suggested to play key roles in mammalian cell differentiation, the cell cycle and circadian regulation, hypoxia response, and carcinogenesis. Here we show that DEC1 overexpression exhibits delayed wound healing and reduces cell proliferation, migration, and invasion. DEC1 strongly repressed the promoter activity of cyclin D1. We further identify a possible DEC-response element in the cyclin D1 promoter region, and confirmed the direct binding of DEC1 to that element. Forced expression of DEC1 efficiently repressed the cyclin D1 promoter and expression. Our clinical data provide the first evidence that there is a strong inverse correlation between DEC1 and cyclin D1 expression in oral cancer, and DEC1 expression significantly correlated with clinicopathological parameters. We suggest that radiation-induced DEC1 overexpression and Akt phosphorylation in cancer cells are mediated via PI-3K signalling. Overexpression of DEC1 activates the PI-3K/Akt signalling pathway through reactive oxygen species (ROS).
authors.affiliation: Research Institute of Occlusion Medicine and Open Research Center, Kanagawa Dental College, Yokosuka, Japan. bhawal.ujjal.kumar@nihon-u.ac.jp
authors.forename: Ujjal K
authors.initials: UK
authors.lastname: Bhawal
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Sato
authors.forename: Yuki
authors.initials: Y
authors.lastname: Arakawa
authors.forename: Katsumi
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanimoto
authors.forename: Yumi
authors.initials: Y
authors.lastname: Ito
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sasahira
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakurai
authors.forename: Masaru
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Isamu
authors.initials: I
authors.lastname: Kashima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kijima
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Abiko
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
authors.forename: Sadao
authors.initials: S
authors.lastname: Sato
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000502:physiology; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics / Q000528:radiation effects
chemical_list: C403671:DELEC1 protein, human; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1