title: Role of c-Jun N-terminal kinase isoforms in the cellular activity of melanoma cell lines.
abstract: BACKGROUND
  The c-Jun N-terminal kinase (JNK) is thought to be involved in inflammation, proliferation and apoptosis.
  
  
  OBJECTIVE
  To examine the role of JNK isoforms in metastasis, proliferation, migration and invasion of the malignant melanoma (MM) cell lines SK-MEL-28, SK-MEL-3 and WM164, using a kinase-specific inhibitor or isoform-specific small interfering (si)RNAs.
  
  
  RESULTS
  SK-MEL-3, a cell line established from metastatic MM, showed slightly increased phosphorylation of both JNK1 and JNK2, whereas WM164, a cell line derived from primary MM, showed significant phosphorylation of JNK1. A JNK inhibitor, SP600125, inhibited cell proliferation of SK-MEL-3 but not SK-MEL-28 or WM164. Transfection of JNK1-specific siRNA reduced the migratory activity of WM164 cells, while silencing of either JNK1 or JNK2 strongly suppressed the invasive activity of SK-MEL-3.
  
  
  CONCLUSIONS
  Our study suggests that JNK isoforms have different roles in MM. Metastasis of MM may be regulated by JNK2, while invasion is regulated by both JNK1 and JNK2. JNK1 and JNK2 respectively mediate cell migration and cell proliferation. Further understanding of the specific roles of JNK isoforms in the pathogenesis of MM may lead to the development of therapies targeting specific isoforms.
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kogushi-Nishi
authors.forename: M
authors.initials: M
authors.lastname: Jinnin
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: F C
authors.initials: FC
authors.lastname: Muchemwa
authors.forename: A
authors.initials: A
authors.lastname: Hirano
authors.forename: T
authors.initials: T
authors.lastname: Makino
authors.forename: S
authors.initials: S
authors.lastname: Fukushima
authors.forename: S
authors.initials: S
authors.lastname: Masuguchi
authors.forename: T
authors.initials: T
authors.lastname: Ishihara
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: H
authors.initials: H
authors.lastname: Ihn
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D048055:Mitogen-Activated Protein Kinase 8 / Q000502:physiology*; D048056:Mitogen-Activated Protein Kinase 9 / Q000502:physiology*; D009361:Neoplasm Invasiveness; D020033:Protein Isoforms / Q000502:physiology; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology
chemical_list: D000873:Anthracenes; D020033:Protein Isoforms; C432165:pyrazolanthrone; D048056:Mitogen-Activated Protein Kinase 9; D048031:JNK Mitogen-Activated Protein Kinases; D048055:Mitogen-Activated Protein Kinase 8