title: Transcription Factor MafB Promotes Hepatocellular Carcinoma Cell Proliferation through Up-Regulation of Cyclin D1.
abstract: OBJECTIVE
  MafB, a member of the Maf transcription factor family, plays a key role in the regulation of pancreatic alpha and beta cell differentiation. However, its function in the control of cancer cell proliferation remains unknown.
  
  
  METHODS
  The mRNA and protein expression levels of MafB in hepatocellular carcinoma tissues and adjacent non-tumor normal specimens were determined by real-time RT-PCR and Western blot, respectively. Report assay was performed to determine whether the regulation of Cyclin D1 by MafB is at the transcriptional level. The binding of MafB to the Cyclin D1 promoter was determined by Chromatin Immunoprecipitation (ChIP) assays. To determine the potential oncogenic effects of MafB in vivo, HepG2 cells transfected with adenovirus containing empty vector or MafB were injected subcutaneously to the skin under the front legs of the nude mice.
  
  
  RESULTS
  In the current study, we showed that MafB was markedly up-regulated in hepatocellular carcinoma (HCC) tissues and cells. Enforced overexpression of MafB enhanced, while its deficiency inhibited HCC cell proliferation. Mechanistically, Cyclin D1, an important regulator of cell cycle progression, was identified as a direct transcriptional target of MafB. Consistently, knockdown of Cyclin D1 largely attenuated the proliferative roles of MafB in HCC cells. Importantly, MafB overexpression significantly promoted cancer cell growth in mice.
  
  
  CONCLUSIONS
  Collectively, our results identified a novel HCC regulatory pathway involving MafB and Cyclin D1, the dysfunction of which drives proliferative character in HCC.
authors.affiliation: Department of general surgery, the fourth affiliated hospital of China medical university, Shenyang, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.forename: Hong-Lei
authors.initials: HL
authors.lastname: Jiang
authors.forename: Dong
authors.initials: D
authors.lastname: Xu
authors.forename: Jun-Zhe
authors.initials: JZ
authors.lastname: Jin
authors.forename: Zhe-Ming
authors.initials: ZM
authors.lastname: Zhao
authors.forename: Yan-Dong
authors.initials: YD
authors.lastname: Ma
authors.forename: Jian
authors.initials: J
authors.lastname: Liang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051258:MafB Transcription Factor / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D015854:Up-Regulation
chemical_list: C490407:MAFB protein, human; D051258:MafB Transcription Factor; D019938:Cyclin D1