title: Induction of urokinase-type plasminogen activator, interleukin-8 and early growth response-1 by STI571 through activating mitogen activated protein kinase in human small cell lung cancer cells.
abstract: We previously demonstrated the simultaneous induction of urokinase-type plasminogen activator and interleukin-8, a CXC chemokine, in doxorubicin-treated human NCI-H69 small cell lung cancer cells in which extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase might be involved. NCI-H69 cells expressed one of the receptor tyrosine kinases, c-Kit, and STI571 inhibited the cell growth and stem cell factor-induced phosphorylation of c-Kit. We therefore investigated the effects of STI571 on the expression of urokinase-type plasminogen activator and interleukin-8 in NCI-H69 cells. Microarray analysis revealed the gene induction of not only urokinase-type plasminogen activator and interleukin-8, but also early growth response-1 in STI571-treated cells. Treatment with STI571 resulted in the induction of phosphorylation of all three mitogen-activated protein kinases, such as extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase and stress-activated protein kinase/c-jun N-terminal protein kinase. U0126, an inhibitor against extracellular signal-regulated kinase 1/2, however, only inhibited the STI571-induced interleukin-8 accumulation. Urokinase-type plasminogen activator and interleukin-8 are important biological factors in tumor cell regulation; STI571 may therefore influence many aspects of tumor cell biology through inducing urokinase-type plasminogen activator and interleukin-8, in which the induction of early growth response-1 expression and extracellular signal-regulated kinase 1/2 phosphorylation might be involved.
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Medical School, Okayama, Japan. c-yoshi@md.okayama-u.ac.jp
authors.forename: Chikamasa
authors.initials: C
authors.lastname: Yoshida
authors.forename: Kenji
authors.initials: K
authors.lastname: Niiya
authors.forename: Masami
authors.initials: M
authors.lastname: Niiya
authors.forename: Misako
authors.initials: M
authors.lastname: Shibakura
authors.forename: Noboru
authors.initials: N
authors.lastname: Asaumi
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
mesh_terms: D001549:Benzamides; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate; D016209:Interleukin-8 / Q000096:biosynthesis*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020411:Oligonucleotide Array Sequence Analysis; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D015533:Transcriptional Activation; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis*
chemical_list: D001549:Benzamides; C508606:CXCL8 protein, human; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D016209:Interleukin-8; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D048049:Extracellular Signal-Regulated MAP Kinases; D014568:Urokinase-Type Plasminogen Activator