IMR90 ER:RAS: A Cell Model of Oncogene-Induced Senescence

Methods Mol Biol. 2019;1896:83-92. doi: 10.1007/978-1-4939-8931-7_9.

Abstract

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).

Keywords: BrdU; Growth arrest; Oncogene-induced senescence; SASP; Senescence; p16INK4a; p21CIP1; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cellular Senescence*
  • Estrogen Antagonists / pharmacology
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Humans
  • Phenotype
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Signal Transduction
  • Tamoxifen / pharmacology
  • ras Proteins / genetics
  • ras Proteins / metabolism*

Substances

  • Estrogen Antagonists
  • Receptors, Estrogen
  • Tamoxifen
  • ras Proteins