title: [Regulation of p14(ARF) expression and induction of cell apoptosis with c-myc in a p53-independent pathway].
abstract: OBJECTIVE
  To explore the regulation of p14(ARF) expression and induction of cell apoptosis with the mutant and wild-type c-myc genes in a p53-independent pathway of signal transduction.
  
  
  METHODS
  The mutant and wild-type c-myc genes were transfected by lentivirus into HCC1937 to form the stable over-expression cell lines. Uninfected cells and lentivirus-infected ones carrying no c-myc gene acted as blank and infection controls respectively. And c-myc and p14(ARF) mRNA and protein, proliferation and apoptosis in HCC1937 with mutant and wild-type c-myc were detected by reverse transcription (RT)-PCR, Western blotting, thiazolyl blue tetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase mediated X-dUTP nick end labeling (TUNEL) respectively.
  
  
  RESULTS
  After the lentivirus-mediated gene transfer, c-myc mRNA and protein expression increased in the mutant and wild-type groups. p14(ARF) mRNA and protein increased in the wild-type group and the mutant group and there were significant difference between them with blank and infection controls (mutant groups: 0.560 ± 0.010, 0.154 ± 0.011, wild-type groups: 0.651 ± 0.010, 0.382 ± 0.013, both P < 0.05). The group of mutant and wild-type c-myc could promote the proliferation of cell growth. And c-myc was more effective to induce apoptosis in the wild-type group as compared with the mutant group (7.1% ± 0.7% vs 3.2% ± 0.4%, P < 0.05).
  
  
  CONCLUSIONS
  In a p53-independent pathway, the over-expression of wild-type c-myc obviously up-regulates the expression of p14(ARF). And cell apoptosis may be induced through the regulation of p14(ARF)-related gene, keep balance of proliferative promotion and apoptosis induction. When there is a loss-of-function of mutant c-myc, tumorigenicity increases via a disturbed balance of proliferative promotion and apoptosis induction.
authors.affiliation: Medical College of Qingdao University, Qingdao 266071, China.
authors.forename: Xiang-juan
authors.initials: XJ
authors.lastname: Liu
authors.forename: Fu-nian
authors.initials: FN
authors.lastname: Li
authors.forename: Dan-dan
authors.initials: DD
authors.lastname: Jiang
authors.forename: Xin-gang
authors.initials: XG
authors.lastname: Wang
authors.forename: Xiang-ping
authors.initials: XP
authors.lastname: Liu
authors.forename: Dian-liang
authors.initials: DL
authors.lastname: Zhang
authors.forename: Chun-hui
authors.initials: CH
authors.lastname: Meng
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis; D002455:Cell Division; D045744:Cell Line, Tumor; D017353:Gene Deletion; D016259:Genes, myc; D016158:Genes, p53; D005822:Genetic Vectors; D006801:Humans; D015398:Signal Transduction; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics* / Q000378:metabolism
chemical_list: D025803:Tumor Suppressor Protein p14ARF