title: Epigenetic regulation ofAPCin the molecular pathogenesis of gallbladder cancer.
abstract: OBJECTIVE
  Loss of function of adenomatous polyposis coli (APC) has been reported in cancer. The two promoters of APC, 1A and 1B also have roles in cancer. But, the epigenetic role of APC promoters is not yet clear in gallbladder cancer (GBC) and gallstone diseases (GSD). We undertook this study to determine the epigenetic role of APC in GBC and GSD.
  
  
  METHODS
  Methylation-specific (MS)-PCR was used to analyze the methylation of APC gene. The expression of APC gene was studied by semi-quantitative PCR, real-time PCR and immunohistochemistry (IHC) in GBC, GSD and adjacent normal tissues.
  
  
  RESULTS
  Of the two promoters, APC 1A promoter was found methylated in 96 per cent GBC ( P=0.0155) and 80 per cent GSD (P=0.015). Exon 1 was downregulated in grade II (P=0.002) and grade III (P=0.0001) of GBC, while exon 2 was normally expressed. Scoring analysis of IHC revealed 0 or negativity in 34.48 per cent (P=0.057) and 1+ in 24.14 per cent (P=0.005) GBC cases suggesting loss of APC expression.
  
  
  CONCLUSIONS
  The present findings indicate epigenetic silencing of APC in advanced GBC. The methylation pattern, followed by expression analysis of APC may be suggested for diagnostic, prognostic and therapeutic purposes in GBC in future.
authors.affiliation: Centre for Genomics; School of Studies in Zoology, Jiwaji University, Gwalior, Madhya Pradesh, India.
authors.forename: Dinesh Singh
authors.initials: DS
authors.lastname: Tekcham
authors.affiliation: Centre for Genomics, Jiwaji University, Gwalior, Madhya Pradesh, India.
authors.forename: Satish S
authors.initials: SS
authors.lastname: Poojary
authors.affiliation: Centre for Genomics, Jiwaji University, Gwalior, Madhya Pradesh, India.
authors.forename: Shushruta
authors.initials: S
authors.lastname: Bhunia
authors.affiliation: Centre for Genomics, Jiwaji University, Gwalior, Madhya Pradesh, India.
authors.forename: Mustafa Ahmed
authors.initials: MA
authors.lastname: Barbhuiya
authors.affiliation: Department of Pathology, Cancer Hospital and Research Institute, Gwalior, Madhya Pradesh, India.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Surgical Oncology, Cancer Hospital and Research Institute; Department of Surgery, Gajra Raja Medical College, Gwalior, Madhya Pradesh, India.
authors.forename: Braj Raj
authors.initials: BR
authors.lastname: Shrivastav
authors.affiliation: Centre for Genomics; School of Studies in Zoology, Jiwaji University, Gwalior, Madhya Pradesh, India.
authors.forename: Pramod Kumar
authors.initials: PK
authors.lastname: Tiwari
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000328:Adult; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005091:Exons; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D046888:Tissue Array Analysis
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein