title: Bioenergetics of lung tumors: alteration of mitochondrial biogenesis and respiratory capacity.
abstract: Little is known on the metabolic profile of lung tumors and the reminiscence of embryonic features. Herein, we determined the bioenergetic profiles of human fibroblasts taken from lung epidermoid carcinoma (HLF-a) and fetal lung (MRC5). We also analysed human lung tumors and their surrounding healthy tissue from four patients with adenocarcinoma. On these different models, we measured functional parameters (cell growth rates in oxidative and glycolytic media, respiration, ATP synthesis and PDH activity) as well as compositional features (expression level of various energy proteins and upstream transcription factors). The results demonstrate that both the lung fetal and cancer cell lines produced their ATP predominantly by glycolysis, while oxidative phosphorylation was only capable of poor ATP delivery. This was explained by a decreased mitochondrial biogenesis caused by a lowered expression of PGC1alpha (as shown by RT-PCR and Western blot) and mtTFA. Consequently, the relative expression of glycolytic versus OXPHOS markers was high in these cells. Moreover, the re-activation of mitochondrial biogenesis with resveratrol induced cell death specifically in cancer cells. A consistent reduction of mitochondrial biogenesis and the subsequent alteration of respiratory capacity was also observed in lung tumors, associated with a lower expression level of bcl2. Our data give a better characterization of lung cancer cells' metabolic alterations which are essential for growth and survival. They designate mitochondrial biogenesis as a possible target for anti-cancer therapy.
authors.affiliation: INSERM U688, Bordeaux, France.
authors.forename: N
authors.initials: N
authors.lastname: Bellance
authors.forename: G
authors.initials: G
authors.lastname: Benard
authors.forename: F
authors.initials: F
authors.lastname: Furt
authors.forename: H
authors.initials: H
authors.lastname: Begueret
authors.forename: K
authors.initials: K
authors.lastname: Smolková
authors.forename: E
authors.initials: E
authors.lastname: Passerieux
authors.forename: J P
authors.initials: JP
authors.lastname: Delage
authors.forename: J M
authors.initials: JM
authors.lastname: Baste
authors.forename: P
authors.initials: P
authors.lastname: Moreau
authors.forename: R
authors.initials: R
authors.lastname: Rossignol
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D048708:Cell Growth Processes; D002460:Cell Line; D019069:Cell Respiration; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005333:Fetus; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008168:Lung; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics; D010085:Oxidative Phosphorylation; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D024101:Mitochondrial Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D019253:Proto-Oncogene Proteins c-bcl-2; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; D000255:Adenosine Triphosphate; D017346:Protein Serine-Threonine Kinases