Induction and Detection of Oncogene-Induced Cellular Senescence in Drosophila.
Cellular senescence is induced by various cellular stresses, including activation of the Ras oncogene. In Drosophila imaginal epithelia, clones of cells expressing oncogenic Ras (RasV12) show several markers of cellular senescence, such as elevation of SA-β-gal activity, upregulation of the Cdk inhibitor Dacapo (Dap), and heterochromatinization. However, these cells do not undergo cell cycle arrest or exhibit a DNA damage response (DDR), cellular hypertrophy, or a senescence-associated secretory phenotype (SASP), other essential markers of cellular senescence. However, we found that inducing mitochondrial dysfunction within RasV12-expressing cells caused all above-mentioned aspects of cellular senescence. This provided the first evidence that cellular senescence occurs in invertebrates and is intriguing because mitochondrial dysfunction is frequently observed in human cancers. Here, we describe the procedures for the induction and detection of cellular senescence in Drosophila epithelia.
Laboratory of Genetics, Graduate School of Biostudies, Kyoto University, Yoshida-Konoecho-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Mai
M
Nakamura
Laboratory of Genetics, Graduate School of Biostudies, Kyoto University, Yoshida-Konoecho-cho, Sakyo-ku, Kyoto, 606-8501, Japan. igaki@lif.kyoto-u.ac.jp.|PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan. igaki@lif.kyoto-u.ac.jp.
Tatsushi
T
Igaki
D000818:Animals; D016922:Cellular Senescence / Q000235:genetics; D004249:DNA Damage; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D055786:Gene Knockout Techniques; D017930:Genes, Reporter; D011905:Genes, ras / Q000235:genetics; D006657:Histones / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009857:Oncogenes; D001616:beta-Galactosidase / Q000378:metabolism
D006657:Histones; D001616:beta-Galactosidase
Cellular senescence; Drosophila; Mitochondrial dysfunction; Ras; SASP