Early BrdU-responsive genes constitute a novel class of senescence-associated genes in human cells.
We identified genes that immediately respond to 5-bromodeoxyuridine (BrdU) in SUSM-1, an immortal fibroblastic line, with DNA microarray and Northern blot analysis. At least 29 genes were found to alter gene expression greater than twice more or less than controls within 36 h after addition of BrdU. They took several different expression patterns upon addition of BrdU, and the majority showed a significant alteration within 12 h. When compared among SUSM-1, HeLa, and TIG-7 normal human fibroblasts, 19 genes behaved similarly upon addition of BrdU. In addition, 14 genes, 9 of which are novel as regards senescence, behaved similarly in senescent TIG-7 cells. The genes do not seem to have a role in proliferation or cell cycle progression. These results suggest that the early BrdU-responsive genes represent early signs of cellular senescence and can be its new biomarkers.
Minagawa
Sachi
S
Kihara Institute for Biological Research and Graduate School of Integrated Science, Yokohama City University, Maioka-cho 641-12, Yokohama 244-0813, Japan.
Nakabayashi
Kazuhiko
K
Fujii
Michihiko
M
Scherer
Stephen W
SW
Ayusawa
Dai
D
D001973:Bromodeoxyuridine / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics*; D004247:DNA / Q000032:analysis / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D017781:Genes, Immediate-Early / Q000187:drug effects* / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D013997:Time Factors
D005819:Genetic Markers; D004247:DNA; D001973:Bromodeoxyuridine