title: Effects of the tyrosine kinase inhibitor imatinib on neuroendocrine tumor cell growth.
abstract: OBJECTIVE
  We investigated the effects of the tyrosine kinase inhibitor imatinib (Gleevec) on neuroendocrine tumor cells.
  
  
  METHODS
  Neuroendocrine tumor cells were incubated without and with imatinib. The effects on growth were examined by methylthiazoletetrazolium (MTT) assay. The c-Kit expression in human endocrine tumor tissue and cell lines was determined by immunohistochemistry and Western blot analysis, respectively. Cytotoxicity assay was performed by fluorescence-activated cell sorting. The telomerase activity was determined using the telomeric repeat amplification protocol.
  
  
  RESULTS
  28% of the insulinomas, 100% of the gastrinomas, and 38% of the carcinoids expressed c-Kit. Imatinib at concentrations >5 microM inhibited cell proliferation and induced apoptosis in both c-Kit-positive and c-Kit-negative cell lines. The PI-3K inhibitor wortmannin did not enhance the effects of imatinib. Imatinib did not sensitize endocrine tumor cells to doxorubicin and 5-fluorouracil. Imatinib inhibited the telomerase activity.
  
  
  CONCLUSIONS
  Imatinib inhibits neuroendocrine tumor cell growth independently of c-Kit by inhibition of other tyrosine kinases or through tyrosine kinase independent pathways.
authors.affiliation: Clinical Research Unit for Gastrointestinal Endocrinology, Department of Gastroenterology, Endocrinology and Metabolism, University of Marburg, DE-35043 Marburg, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Lankat-Buttgereit
authors.forename: Dieter
authors.initials: D
authors.lastname: Hörsch
authors.forename: Peter
authors.initials: P
authors.lastname: Barth
authors.forename: Rudolf
authors.initials: R
authors.lastname: Arnold
authors.forename: Silke
authors.initials: S
authors.lastname: Blöcker
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Göke
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D011743:Pyrimidines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit