IMR90 ER:RAS: A Cell Model of Oncogene-Induced Senescence
Oncogene-induced senescence (OIS) is a cellular response that limits the replication of cells expressing oncogenes. As a result, OIS is a potent tumor suppressor mechanism limiting cancer progression. Here we describe IMR90 ER:RAS, a widely used model to study OIS in cell culture. This model takes advantage of IMR90 human primary fibroblast infected with a 4-hydroxy-tamoxifen (4-OHT) inducible ER:RAS construct. RAS activation upon 4-OHT treatment results in a coordinated induction of senescence, recapitulating different aspects of the phenotype such as the growth arrest and the establishment of a senescence-associated secretory phenotype (SASP).
Key wordsSenescence Oncogene-induced senescence SASP p53 p21CIP1 p16INK4a Growth arrest BrdU
This work was supported by core funding from the Medical Research Council, London Institute of Medical Sciences. A.J.I. is supported by a National Institute for Health Research (NIHR) Clinical Lectureship, and acknowledges support from the NIHR and Imperial Biomedical Research Centre (BRC).