title: Leptin Inhibits the Apoptosis of Endometrial Carcinoma Cells Through Activation of the Nuclear Factor κB-inducing Kinase/IκB Kinase Pathway.
abstract: OBJECTIVE
  Leptin has recently been shown to affect cancer proliferation and invasion through multiple pathways. In the current study, we investigated the role of leptin in endometrial carcinoma (EC) apoptosis and the underlying mechanisms of action.
  
  
  METHODS
  Immunoprecipitation was used to characterize leptin receptor expression in EC lines. The levels of nuclear factor κB-inducing kinase (NIK)/IκB kinase (IKK) signaling proteins were analyzed using Western blot. In addition, Western blot and immunohistochemical analyses were used to detect the hierarchy of these proteins in EC tissues. Quantitative cancer cell apoptosis assay was performed using flow cytometry after incubation of cells with Annexin-V/fluorescein/propidium iodide, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide or staining of cancer cell DNA fragments with propidium iodide.
  
  
  RESULTS
  Leptin induced a decrease in apoptosis in Ishikawa and HEC-1A EC cells, partly through nuclear factor κB activation via phosphorylation in the IKK/NIK pathway. Inhibition of IKK or NIK partly neutralized this suppression of apoptosis. Expression levels of leptin receptors (Ob-Rs) and IKK/NIK signaling proteins were higher in poorly and moderately differentiated than in well-differentiated EC tissues, and higher Ob-Rs expression was observed in clinical stages II and III, compared with stage I EC (P = 0.012). High serum leptin concentration displayed mild correlation (r = 0.23, P = 0.035) with degree of EC differentiation.
  
  
  CONCLUSIONS
  Leptin inhibits EC apoptosis partly through activation of the NIK/IKK pathway in vitro. Ob-Rb overexpression seems to facilitate EC progression.
authors: *Department of Radiation Oncology, The First Affiliated Hospital of the Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China; and †Department of Obstetrics and Gynecology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
authors: Xi
authors: X
authors: Zhou
authors: Hui
authors: H
authors: Li
authors: Yanlan
authors: Y
authors: Chai
authors: Zi
authors: Z
authors: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D015992:Body Mass Index; D049109:Cell Proliferation / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D020738:Leptin / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D009367:Neoplasm Staging; D010766:Phosphorylation / Q000187:drug effects; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D054411:Receptors, Leptin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D051550:I-kappa B Kinase; D020738:Leptin; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D054411:Receptors, Leptin; D000097782:NF-kappaB-Inducing Kinase; C515448:LEPR protein, human