title: Cullin7: a new gene involved in liver carcinogenesis related to metabolic syndrome.
abstract: BACKGROUND
  Metabolic syndrome (MS) is an emerging risk factor in hepatocellular carcinoma (HCC). HCC related to MS may occur either in advanced fibrosis or before the development of cirrhosis, suggesting involvement of different molecular pathways according to the features of background liver.
  
  
  OBJECTIVE
  To investigate genomic aberrations in HCC related to MS in order to identify new target genes involved in liver carcinogenesis.
  
  
  METHODS
  Chromosomal aberrations of HCC obtained from 20 patients with MS (HCC/MS) were studied by comparative genomic hybridisation and compared with HCC related to hepatitis C virus (HCV) infection (HCC/HCV, n=10) and, within the group of HCC with MS, according to the condition of the background liver (presence or absence of significant fibrosis).
  
  
  RESULTS
  Among the most frequent chromosomal alterations observed in HCC, 6p21.1 amplification had a higher incidence in HCC/MS than in HCC/HCV (60% vs 20%, p<0.01). Advanced fibrosis/cirrhosis in the peritumoral liver was the only clinicopathological factor associated with the 6p21.1 amplicon in HCC/MS. Increased expression of cullin7 (CUL7), a gene located at the 6p21.1 locus, was demonstrated in HCC with the 6p21.1 amplicon, in parallel with a decrease in cyclin D1 expression. CUL7 downregulation using siRNA transfection in hepatoma cell lines induced significant cyclin D1 expression (by promoting its degradation), decreased cell proliferation and increased apoptosis.
  
  
  CONCLUSIONS
  This study demonstrates specific genomic alterations in HCC/MS and points to CUL7 as a novel gene potentially involved in liver carcinogenesis associated with MS, the amplification of which might influence cell proliferation.
authors.affiliation: Pathology Department, Beaujon Hospital, 100 boulevard du Général Leclerc, Clichy 92118, France. vparadis@teaser.fr
authors.forename: Valerie
authors.initials: V
authors.lastname: Paradis
authors.forename: Miguel
authors.initials: M
authors.lastname: Albuquerque
authors.forename: Mouniya
authors.initials: M
authors.lastname: Mebarki
authors.forename: Lucie
authors.initials: L
authors.lastname: Hernandez
authors.forename: Stephane
authors.initials: S
authors.lastname: Zalinski
authors.forename: Samuel
authors.initials: S
authors.lastname: Quentin
authors.forename: Jacques
authors.initials: J
authors.lastname: Belghiti
authors.forename: Jean
authors.initials: J
authors.lastname: Soulier
authors.forename: Pierre
authors.initials: P
authors.lastname: Bedossa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002869:Chromosome Aberrations; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D044842:Cullin Proteins / Q000235:genetics* / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications*; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C506299:CUL7 protein, human; D044842:Cullin Proteins; D019938:Cyclin D1