title: MEK1 and MEK2 differentially regulate human insulin- and insulin glargine-induced human bladder cancer T24 cell proliferation.
abstract: BACKGROUND
  Increased risk of bladder cancer has been reported in diabetic patients. This study was to investigate the roles of mitogen-activated protein kinase kinase (MEK) 1 and 2 in the regulation of human insulin- and insulin glargine-induced proliferation of human bladder cancer T24 cells.
  
  
  METHODS
  In the absence or presence of a selective inhibitor for MEK1 (PD98059) or a specific siRNA for MEK2 (siMEK2), with or without addition of insulin or glargine, T24 cell proliferation was evaluated by cell counting kit (CCK)-8 assay. Protein expression of MEK2, phosphorylation of ERK1/2 and Akt was analyzed by Western blotting.
  
  
  RESULTS
  T24 cell proliferation was promoted by PD98059 at 5 - 20 µmol/L, inhibited by siMEK2 at 25 - 100 nmol/L. PD98059 and siMEK2 remarkably reduced phosphorylated ERK1/2. Insulin- and glargine-induced T24 cell proliferation was enhanced by PD98059, suppressed while not blocked by siMEK2. Insulin- and glargine-induced ERK1/2 activation was blocked by PD98059 or siMEK2 treatment, whereas activation of Akt was not affected.
  
  
  CONCLUSIONS
  MEK1 inhibits while MEK2 contributes to normal and human insulin- and insulin glargine-induced human bladder cancer T24 cell proliferation.
authors.affiliation: Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China.
authors.forename: Shan-Ying
authors.initials: SY
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.forename: Tian-Xin
authors.initials: TX
authors.lastname: Lin
authors.forename: Fang
authors.initials: F
authors.lastname: Su
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Liang
authors.forename: Heemann
authors.initials: H
authors.lastname: Uwe
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000494:pharmacology*; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048370:MAP Kinase Kinase 2 / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics / Q000502:physiology; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D007328:Insulin; D049528:Insulin, Long-Acting; D034741:RNA, Small Interfering; D000069036:Insulin Glargine; C482128:MAP2K2 protein, human; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one