title: Apoptosis-related molecular differences for response to tyrosin kinase inhibitors in drug-sensitive and drug-resistant human bladder cancer cells.
abstract: BACKGROUND
  The epidermal growth factor receptor (EGFR) family is reportedly overexpressed in bladder cancer, and tyrosine kinaseinhibitors (TKIs) have been suggested as treatment. Gefitinib is a selective inhibitor of the EGFR and lapatinib is a dual inhibitor of both the EGFR and HER2 (human EGFR type 2 receptor). Both compounds compete with the binding of adenosine triphosphate (ATP) to the tyrosine kinase domain of the respective receptors to inhibit receptor autophosphorylation causing suppression of signal transduction. Unfortunately, resistance to these inhibitors is a major clinical problem.
  
  
  OBJECTIVE
  To compare the apoptosis signaling pathway(s) induced by gefitinib and lapatinib, in UM-UC-5 (drug-sensitive) and UM-UC-14 (drug-resistant) bladder cancer cells and to identify molecular differences that might be useful predictors of their efficacy.
  
  
  METHODS
  Cell proliferation, cell cycle and apoptosis assay were used to detect the effect of TKIs on UM-UC-5 and UM-UC-14 cells. Molecular differences for response to TKIs were examined by protein array.
  
  
  RESULTS
  TKIs strongly inhibited cell proliferation and induced cell cycle G1 arrest and apoptosis in UM-UC-5 cells. Most notable apoptosis molecular differences included decreased claspin, trail, and survivin by TKIs in the sensitive cells. In contrast, TKIs had no effect on resistant cells.
  
  
  CONCLUSIONS
  Claspin, trail, and survivin might be used to determine the sensitivity of bladder cancers to TKIs.
authors: Jixia
authors: J
authors: Li
authors: Bo
authors: B
authors: Lv
authors: Xiangyong
authors: X
authors: Li
authors: Zhiwei
authors: Z
authors: He
authors: Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical College, Dongguan, China.
authors: Keyuan
authors: K
authors: Zhou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D000077156:Gefitinib; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis*; D000077341:Lapatinib; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000255:Adenosine Triphosphate; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000077156:Gefitinib; D051034:Inhibitor of Apoptosis Proteins; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand; C107489:BIRC5 protein, human; C488158:CLSPN protein, human; C505653:TNFSF10 protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human