Cooperative effect of antisense-Rb and antisense-p53 oligomers on the extension of life span in human diploid fibroblasts, TIG-1.
Normal human diploid fibroblasts, TIG-1, which have a replicative life span of about 62 population doublings (PD), tended to senesce after about 50 PD with a gradual decrease in sensitivity to serum. Treatment of TIG-1 cells with the antisense-Rb oligomer, which completely depleted the retinoblastoma susceptibility gene product (RB), extended life span by about 10 PD. Treatment with the antisense-p53 oligomer alone had no effect; however, cotreatment with the antisense-Rb oligomer further potentiated the extension and the increased sensitivity to serum caused by the antisense-Rb oligomer alone, suggesting that p53 and RB function in separate, yet complementary pathways in signal transduction to senescence. The c-fos expression, which is presumed to be regulated negatively by RB, was not stimulated in partially senescent TIG-1 cells by treatment with the antisense-Rb oligomer.
Hara
E
E
Department of Applied Biological Science, Science University of Tokyo, Chiba, Japan.
Tsurui
H
H
Shinozaki
A
A
Nakada
S
S
Oda
K
K
D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003062:Codon / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D016161:Genes, Retinoblastoma; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D011519:Proto-Oncogenes / Q000187:drug effects; D016160:Retinoblastoma Protein / Q000235:genetics*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D003062:Codon; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D011505:Protein-Tyrosine Kinases