title: Autophagy and apoptosis-related genes in chronic liver disease and hepatocellular carcinoma.
abstract: BACKGROUND
  Dysregulation of autophagy is important in the pathogenesis of many diseases, including cancer. Several aspects of the biological role of autophagy are however still unclear and the relationship between apoptosis and autophagy, particularly in the liver has yet to be thoroughly explored. In this study we evaluated the expression of Beclin 1 (one of the main autophagocytic agents, which bridges autophagy, apoptosis and both differentiation), and both pro- (Bad, Bax) and anti-apoptotic (Bcl-2, Bcl-xL) factors in liver samples from patients with different stages of liver disease.
  
  
  METHODS
  The study concerned 93 patients from 49 cases of chronic hepatitis (CH) (30 HCV and 19 HBV-related), 13 of cirrhosis (CIRR) (10 HCV and 3 HBV-related), 21 of hepatocellular carcinoma (both HCC and peritumoral tissues [PHCC]), and 10 controls (CONTR). Real-time PCR and Western blotting were used to measure mRNA and protein expression levels.
  
  
  RESULTS
  Beclin 1 mRNA levels were lower in HCC than in CH (P = 0.010) or CIRR (P = 0.011), and so were the Bcl-xL transcripts (P < 0.0001). Bad mRNA levels were higher in CH and CIRR than in CONTR, while Bax transcripts were increased in all tissues (P = 0.036). PHCC expressed the highest Bcl-2 mRNA levels. HBV-related CH tissues showed significantly higher Bcl-xL and Bad mRNA levels than HCV-related CH (P = 0.003 and P = 0.016, respectively).
  
  
  CONCLUSIONS
  High Beclin 1, Bcl-xL and Bad levels in CH and CIRR tissues suggest an interaction between autophagy and apoptosis in the early and intermediate stages of viral hepatitis. In HCC these processes seem to be downregulated, probably enabling the survival and growth of neoplastic hepatocytes.
authors.affiliation: Department of Surgery, Oncology and Gastroenterology Division of Gastroenterology, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
authors.forename: Andromachi
authors.initials: A
authors.lastname: Kotsafti
authors.forename: Fabio
authors.initials: F
authors.lastname: Farinati
authors.forename: Romilda
authors.initials: R
authors.lastname: Cardin
authors.forename: Umberto
authors.initials: U
authors.lastname: Cillo
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
authors.forename: Marina
authors.initials: M
authors.lastname: Bortolami
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D001343:Autophagy / Q000235:genetics*; D000071186:Beclin-1; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D006509:Hepatitis B / Q000235:genetics; D006526:Hepatitis C / Q000235:genetics; D006521:Hepatitis, Chronic / Q000235:genetics* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D008875:Middle Aged; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D051025:bcl-Associated Death Protein / Q000096:biosynthesis; D051020:bcl-X Protein / Q000096:biosynthesis
chemical_list: D051017:Apoptosis Regulatory Proteins; C494819:BAD protein, human; C494826:BAX protein, human; C494811:BCL2L1 protein, human; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein