Prolonged unbalanced growth induces cellular senescence markers linked with mechano transduction in normal and tumor cells.
Cellular senescence is induced by diverse means and hence thought to be mediated by multiple pathways. We show that prolonged unbalanced growth due to retardation of DNA replication elicits a senescence-like phenomenon irrespective of the cell type. In fact, modest inhibition of DNA replication by various means led to cell swelling, cytoskeletal alterations, and irregularly enlarged, flat cell shape. Such cells upregulated senescence-associated genes, and eventually lost division potential. These phenotypes, which define cellular senescence, were virtually reversed by reducing protein synthesis or blocking ERK of the MAP kinase family. These results suggest that cellular senescence is a manifestation of prolonged unbalanced growth linked with mechano transduction and can be prevented by at least two different ways.
Sumikawa
Emi
E
Kihara Institute for Biological Research and Graduate School of Integrated Science, Yokohama City University, Maioka-cho 641-12, Yokohama 244-0813, Japan.
Matsumoto
Yuko
Y
Sakemura
Risa
R
Fujii
Michihiko
M
Ayusawa
Dai
D
D000199:Actins / Q000737:chemistry; D017209:Apoptosis; D001703:Biophysics / Q000379:methods; D015152:Blotting, Northern; D015153:Blotting, Western; D002453:Cell Cycle; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048430:Cell Shape; D048429:Cell Size; D002470:Cell Survival; D016922:Cellular Senescence; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004261:DNA Replication; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D013997:Time Factors; D001616:beta-Galactosidase / Q000378:metabolism
D000199:Actins; D004247:DNA; D001616:beta-Galactosidase