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Article
Context dependent roles for RB-E2F transcriptional regulation in tumor suppression
PLoS ONE
  • Michael J. Thwaites, Lawson Health Research Institute
  • Matthew J. Cecchini, Western University
  • Daniel T. Passos, Lawson Health Research Institute
  • Komila Zakirova, Lawson Health Research Institute
  • Frederick A. Dick, Lawson Health Research Institute
Document Type
Article
Publication Date
1-1-2019
URL with Digital Object Identifier
10.1371/journal.pone.0203577
Abstract

RB-E2F transcriptional control plays a key role in regulating the timing of cell cycle progression from G1 to S-phase in response to growth factor stimulation. Despite this role, it is genetically dispensable for cell cycle exit in primary fibroblasts in response to growth arrest signals. Mice engineered to be defective for RB-E2F transcriptional control at cell cycle genes were also found to live a full lifespan with no susceptibility to cancer. Based on this background we sought to probe the vulnerabilities of RB-E2F transcriptional control defects found in Rb1 R461E,K542E mutant mice (Rb1 G ) through genetic crosses with other mouse strains. We generated Rb1 G/G mice in combination with Trp53 and Cdkn1a deficiencies, as well as in combination with Kras G12D . The Rb1 G mutation enhanced Trp53 cancer susceptibility, but had no effect in combination with Cdkn1a deficiency or Kras G12D . Collectively, this study indicates that compromised RB-E2F transcriptional control is not uniformly cancer enabling, but rather has potent oncogenic effects when combined with specific vulnerabilities.

Citation Information
Michael J. Thwaites, Matthew J. Cecchini, Daniel T. Passos, Komila Zakirova, et al.. "Context dependent roles for RB-E2F transcriptional regulation in tumor suppression" PLoS ONE Vol. 14 Iss. 1 (2019)
Available at: http://works.bepress.com/frederick-dick/11/