title: Autophagy and Bcl-2/BNIP3 death regulatory pathway in non-small cell lung carcinomas.
abstract: We recently showed that non-small cell lung carcinomas (NSCLCs) are of dismal prognosis when encompassing accelerated autophagic activity. The regulation of this abnormally functioning degradation system and its association with hypoxia and apoptosis in lung carcinoma patients is unexplored. In this study we used 115 NSCLC tissues to examine the immunohistochemical expression of four distinct molecules - the major regulator of autophagy Beclin 1, the anti-apoptotic and anti-autophagic protein Bcl-2, the pro-apoptotic and pro-autophagic protein BNIP3, and a marker of hypoxia and glucolysis, the glucose transporter Glut 1. Most cases showed reduced reactivity for Beclin 1 (62%) and Bcl-2 (82%) proteins, almost half of our sample revealed strong BNIP3 expression (57%), whereas most of the carcinomas strongly expressed Glut 1 antigen (71%). Beclin 1 expression showed no association with survival. Bcl-2 positivity was a marker of good prognosis (p = 0.04), whereas BNIP3 (p = 0.0004) and Glut 1 (p = 0.03) expression correlated with poor outcome in Stage I disease. Autophagic status was negatively associated with Bcl-2 (p = 0.0006), but positively with Glut 1 expression (p = 0.001). In conclusion, the accelerated autophagic status in NSCLC is unrelated to Beclin 1 and BNIP3 expression, but does show significant association with Bcl-2 reactivity. Furthermore, we showed important correlations between glucolysis and autophagy, guiding new pathways in future lung carcinoma research.
authors.affiliation: Department of Pathology, Democritus University of Thrace Medical School, Alexandroupolis, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Karpathiou
authors.forename: Efthimios
authors.initials: E
authors.lastname: Sivridis
authors.forename: Michael
authors.initials: M
authors.lastname: Koukourakis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Mikroulis
authors.forename: Demosthenes
authors.initials: D
authors.lastname: Bouros
authors.forename: Marios
authors.initials: M
authors.lastname: Froudarakis
authors.forename: George
authors.initials: G
authors.lastname: Bougioukas
authors.forename: Efstratios
authors.initials: E
authors.lastname: Maltezos
authors.forename: Alexandra
authors.initials: A
authors.lastname: Giatromanolaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; C090121:BNIP3 protein, human; D000071186:Beclin-1; D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; C495677:SLC2A1 protein, human