title: Globular adiponectin and its downstream target genes are up-regulated locally in human colorectal tumors: ex vivo and in vitro studies.
abstract: OBJECTIVE
  Low plasma adiponectin levels are linked to obesity, insulin resistance, and the risk of several types of malignancy. Despite the decline in circulating adiponectin concentrations, the increase in the expression of adiponectin receptors AdipoR1 and AdipoR2 is greater in cancerous than in normal colonic tissue. The purpose of this study was to obtain new information regarding local adiponectin signaling in the pathogenesis of colorectal cancer (CRC).
  
  
  METHODS
  We characterized the expressions of adiponectin and several of its downstream targets in paired samples of tumor tissue and adjacent noncancerous mucosa in 60 surgical patients with colorectal adenocarcinomas.
  
  
  RESULTS
  Adiponectin was expressed in both colorectal tumors and the adjacent mucosa. The expressions of adiponectin mRNA and its globular protein variant (gAd), adiponectin receptor type 1 and 5' AMP-activated protein kinase (AMPK) mRNA were significantly higher in colorectal tumors than in the adjacent mucosa. This finding was accompanied by increased mRNA expression of genes encoding proteins involved in fatty-acid trafficking and oxidation. The potential interference between adiponectin stimulation and AMPK activation through AMPK1 was examined in an in vitro model with the aid of silencing-RNA experiments. Furthermore, AMPK mRNA expression on tumors was positively correlated with a more advanced tumor stage in the patients.
  
  
  CONCLUSIONS
  We propose that the globular adiponectin-AMPK pathway functions in an autocrine manner in colorectal tumors, explaining some of the beneficial changes in cellular oxidative capacity in tumors in favor of tumorigenesis.
authors.affiliation: Department of Clinical Molecular Biology and Laboratory Sciences (EpiGen), Institute for Clinical Medicine, University of Oslo, Norway; Surgical Department, Akershus University Hospital, Lørenskog, Norway. Electronic address: katja@vetvik.org.
authors.forename: Katja Kannisto
authors.initials: KK
authors.lastname: Vetvik
authors.affiliation: Department of Clinical Molecular Biology and Laboratory Sciences (EpiGen), Institute for Clinical Medicine, University of Oslo, Norway.
authors.forename: Tonje
authors.initials: T
authors.lastname: Sonerud
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; Department of Medical Genetics, University of Oslo, Norway.
authors.forename: Mona
authors.initials: M
authors.lastname: Lindeberg
authors.affiliation: Department of Clinical Molecular Biology and Laboratory Sciences (EpiGen), Institute for Clinical Medicine, University of Oslo, Norway.
authors.forename: Torben
authors.initials: T
authors.lastname: Lüders
authors.affiliation: Department of Clinical Molecular Biology and Laboratory Sciences (EpiGen), Institute for Clinical Medicine, University of Oslo, Norway; Surgical Department, Østfold Hospital Trust, Fredrikstad, Norway.
authors.forename: Ragnhild H
authors.initials: RH
authors.lastname: Størkson
authors.affiliation: Department of Clinical Molecular Biology and Laboratory Sciences (EpiGen), Institute for Clinical Medicine, University of Oslo, Norway.
authors.forename: Kristin
authors.initials: K
authors.lastname: Jonsdottir
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; Department of Medical Genetics, University of Oslo, Norway.
authors.forename: Eirik
authors.initials: E
authors.lastname: Frengen
authors.affiliation: Obesity Research Unit, Department of Medicine, Division of Endocrinology, Helsinki University Central Hospital and University of Helsinki, Finland; Institute of Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland.
authors.forename: Kirsi H
authors.initials: KH
authors.lastname: Pietiläinen
authors.affiliation: Department of Clinical Molecular Biology and Laboratory Sciences (EpiGen), Institute for Clinical Medicine, University of Oslo, Norway; Surgical Department, Akershus University Hospital, Lørenskog, Norway; Institute of Health Promotion, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Ida
authors.initials: I
authors.lastname: Bukholm
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D052242:Adiponectin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D046228:Microarray Analysis; D008875:Middle Aged; D017510:Protein Folding; D059467:Transcriptome; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D055372:AMP-Activated Protein Kinases
keywords: AMPK; AdipoR; Colon cancer; Full-length adiponectin; Insulin resistance