title: Direct role of adiponectin and adiponectin receptors in endometrial cancer: in vitro and ex vivo studies in humans.
abstract: Low adiponectin levels are an independent risk factor for and mediate the effect of obesity on endometrial cancer in epidemiology studies. The direct or indirect mechanisms underlying these findings remain to be elucidated. We first examined the expression of adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) in normal human endometrium and in endometrial cancer tissues ex vivo. We then used KLE and RL95-2 human endometrial cancer cell lines in vitro to study relative expression of AdipoRs, to investigate the effect of adiponectin on activating intracellular signaling pathways, and to assess its potential to alter malignant properties. We report for the first time that the relative expression level of AdipoR1 is higher than AdipoR2 in human endometrial cancer tissue, but the expression of AdipoRs is not statistically different from nonneoplastic tissues. We also show for the first time in endometrial cancer cell lines in vitro that adiponectin suppresses endometrial cancer proliferation acting through AdipoRs. Adiponectin also increases the expression of the adaptor molecule LKB1, which is required for adiponectin-mediated activation of AMPK/S6 axis and modulation of cell proliferation, colony formation, adhesion, and invasion of KLE and RL95-2 cell lines. These novel mechanistic studies provide for the first time in vitro and ex vivo evidence for a causal role of adiponectin in endometrial cancer.
authors: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors: Hyun-Seuk
authors: HS
authors: Moon
authors: John P
authors: JP
authors: Chamberland
authors: Konstantinos
authors: K
authors: Aronis
authors: Sofia
authors: S
authors: Tseleni-Balafouta
authors: Christos S
authors: CS
authors: Mantzoros
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D006801:Humans; D009361:Neoplasm Invasiveness; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014410:Tumor Stem Cell Assay
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D034741:RNA, Small Interfering; D054419:Receptors, Adiponectin; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases