title: Engagement of integrinβ1 induces resistance of bladder cancer cells to mitomycin-C.
abstract: OBJECTIVE
  To identify whether integrinβ1 subunit is responsible for the resistance of bladder cancer cell to the therapeutic drug mitomycin-C (MMC), when grown on fibronectin (FN).
  
  
  METHODS
  The expression of integrinβ1 on bladder cancer T24 and 5637 cells was examined by the flow cytometer. The adhesion of cells to plates with the absence or presence of FN was determined. Analysis of apoptosis induced by MMC was assessed using the flow cytometer in combination with an integrinβ1-blocking antibody or siRNA targeting the coding region of integrinβ1. Western blot was used to study the expression change of integrinβ1 and its downstream molecules.
  
  
  RESULTS
  Bladder cancer T24 and 5637 cells express high level of integrinβ1 (87.3% ± 2.3 and 90.1% ± 1.9, respectively). Cellular adhesion to FN was significantly reduced by the blocking of integrinβ1. Blocking or silencing of integrinβ1 significantly abolished the drug resistance of cells grown on FN to MMC (P <.05) and inhibited the activation of survival signals phosphoinositide-3 kinase (PI3-K)/Akt.
  
  
  CONCLUSIONS
  Integrinβ1-mediated cellular adhesion to FN confers drug resistance to MMC on bladder cancer cells. Knockdown of integrinβ1 may abolish the drug resistance phenotype and sensitize bladder cancer cells to MMC.
authors.affiliation: Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Cheng-Jing
authors.initials: CJ
authors.lastname: Zhang
authors.forename: Zhou-Jun
authors.initials: ZJ
authors.lastname: Shen
authors.forename: Chun-Wu
authors.initials: CW
authors.lastname: Pan
authors.forename: Shan
authors.initials: S
authors.lastname: Zhong
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Min-Guang
authors.initials: MG
authors.lastname: Zhang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000503:physiopathology*; D053455:Caspase 10 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D003124:Colorimetry; D003470:Culture Media; D019610:Cytoprotection / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D016685:Mitomycin / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D000903:Antibiotics, Antineoplastic; D003470:Culture Media; D005353:Fibronectins; D019012:Integrin beta1; D016685:Mitomycin; D053455:Caspase 10; D053148:Caspase 3