title: CD80 down-regulation is associated to aberrant DNA methylation in non-inflammatory colon carcinogenesis.
abstract: The lack of positive costimulatory molecules represents one of the mechanisms by which tumor cells evade immune surveillance. Promoter hypermethylation plays a major role in cancer development through transcriptional silencing of critical genes. The aim of this study was to examine the expression of the costimulatory molecule CD80 in relationship with genomic methylation in non-inflammatory colon carcinogenesis.
  
  
  
  Colonic mucosal samples were collected from healthy subjects (n = 30) and from dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b and CD80 mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR. CD80 expression was assessed in HT29, HCT-15 and LoVo cell lines after treatment with the DNA-methyltransferase inhibitor 5-Aza-2'-deoxycytidine.
  
  
  
  CD80 mRNA levels were significantly lower in the non-inflammatory dysplastic colonic mucosa of patients with one or more methylated genes and inversely correlated with patients' methylation scores (τ = -0.41, p = 0.05 and τ = -0.37, p = 0.05, respectively). Treatment with 5-Aza-2'-deoxycytidine significantly increased CD80 expression both in terms of the level of CD80 mRNA (p = 0.007) and of CD80+ cells (p = 0.003).
  
  
  
  These results indicate that the failure of immune surveillance mechanisms in non-inflammatory colon carcinogenesis may be linked to genomic methylation directly or indirectly affecting CD80 expression.
authors.affiliation: Esophageal and Digestive Tract Surgery Unit, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy. marcoscarpa73@yahoo.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Scarpa
authors.affiliation: Esophageal and Digestive Tract Surgery Unit, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy.
authors.forename: Melania
authors.initials: M
authors.lastname: Scarpa
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Ignazio
authors.initials: I
authors.lastname: Castagliuolo
authors.affiliation: Esophageal and Digestive Tract Surgery Unit, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Erroi
authors.affiliation: Esophageal and Digestive Tract Surgery Unit, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Basato
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Brun
authors.affiliation: Department of Surgery, Oncology and Gastroenterology DISCOG, University of Padova, Padova, Italy.
authors.forename: Imerio
authors.initials: I
authors.lastname: Angriman
authors.affiliation: Esophageal and Digestive Tract Surgery Unit, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Castoro
mesh_terms: D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D018122:B7-1 Antigen / Q000235:genetics*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics*; D019175:DNA Methylation; D000077209:Decitabine; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000187:drug effects
chemical_list: D018122:B7-1 Antigen; D000077209:Decitabine; D001374:Azacitidine