title: Decreased c-Myc expression and its involvement in X-ray-induced apoptotic cell death of human T-cell leukaemia cell line MOLT-4.
abstract: OBJECTIVE
  To investigate the possible involvement of c-Myc and ceramide-c-Jun N-terminal kinase (JNK) pathway in X-ray-induced apoptotic cell death of MOLT-4 cells.
  
  
  METHODS
  The expressions of c-Myc protein and c-myc mRNA after X-irradiation were analysed by Western blotting and RT-PCR between radiosensitive MOLT-4 and radioresistant variant Rh-1a cells with less JNK activation than the parental cells. Apoptotic cell death was determined by a dye exclusion test, the appearance of chromatin condensation and DNA fragmentation. The effect of a JNK activator anisomycin or c-Myc inhibitor peptides (Int-H1-S6A, F8A) on the amount of c-Myc protein and on the induction of apoptosis was investigated, respectively.
  
  
  RESULTS
  In X-irradiated MOLT-4 cells, amounts of both c-myc mRNA and c-Myc protein rapidly decreased, which was followed by apoptotic cell death, while little change or limited reduction of c-Myc protein was observed in X-irradiated Rh-1a cells with accompanying higher cell viability. Exposure of MOLT-4 and Rh-1a cells to c-Myc inhibitor peptides similarly induced apoptotic cell death with decreases of c-Myc protein. Anisomycin rapidly induced JNK activation and a subsequent decrease of c-Myc protein, causing cell death in MOLT-4 cells. On the other hand, Rh-1a cells were more resistant to anisomycin than parental MOLT-4 cells, showing less JNK activation and a delayed decrease of c-Myc protein.
  
  
  CONCLUSIONS
  A decrease of c-Myc protein was considered important in X-ray-induced apoptotic cell death of MOLT-4 cells; activation of the JNK pathway caused reduction in the amounts of c-myc mRNA and c-Myc protein, and finally induced apoptotic cell death.
authors.affiliation: Department of Radiation Oncology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Enomoto
authors.forename: N
authors.initials: N
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Kang
authors.forename: K
authors.initials: K
authors.lastname: Hirano
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: J
authors.initials: J
authors.lastname: Zhu
authors.forename: A
authors.initials: A
authors.lastname: Morita
authors.forename: Y
authors.initials: Y
authors.lastname: Hosoi
authors.forename: K
authors.initials: K
authors.lastname: Sakai
authors.forename: H
authors.initials: H
authors.lastname: Koyama
mesh_terms: D000841:Anisomycin / Q000494:pharmacology; D017209:Apoptosis / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D006801:Humans; D015458:Leukemia, T-Cell / Q000473:pathology*; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D014965:X-Rays
chemical_list: C064769:N-acetylsphingosine; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D000841:Anisomycin; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D013110:Sphingosine