Cooperative effect of antisense-Rb and antisense-p53 oligomers on the extension of life span in human diploid fibroblasts, TIG-1

• Published in: Biochemical and biophysical research communications Vol. 179; no. 1; pp. 528 - 534
• Main Authors: Hara, Eiji, Tsurui, Hiromichi, Shinozaki, Ayako, Nakada, Susumu, Oda, Kinichiro
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 30.08.1991; Elsevier
• Subjects: Ageing, cell death; Base Sequence; Biological and medical sciences; Cell Division - drug effects; Cell Line; Cell physiology; Cell Survival - drug effects; Codon - genetics; Fibroblasts - cytology; Fibroblasts - drug effects; Fundamental and applied biological sciences. Psychology; Genes, Retinoblastoma; Humans; Kinetics; Molecular and cellular biology; Molecular Sequence Data; Oligonucleotides, Antisense - pharmacology; Protein-Tyrosine Kinases - genetics; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-fos; Proto-Oncogenes - drug effects; Retinoblastoma Protein - genetics; Time Factors; Tumor Suppressor Protein p53 - genetics; RB; DMEM; SDS; PD; FCS; PDL; HDF; HPV; Human; Lifetime; Senescence; Antisense DNA; Oligodeoxyribonucleotide; Fibroblast; Cooperative phenomenon; Tumor suppressor gene
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/0006-291X(91)91403-Y

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.