A population of BJ fibroblasts escaped from Ras-induced senescence susceptible to transformation

Shinji Kohsaka, Ken Sasai, Kenta Takahashi, Tsuyoshi Akagi, Mishie Tanino, Taichi Kimura, Hiroshi Nishihara, Shinya Tanaka

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


Oncogenic stimuli such as H-Ras induce oncogene-induced senescence (OIS) in fibroblasts to protect against transformation. Here we found that a population of the human diploid fibroblasts can escape from OIS induced by H-RasV12. We designated these OIS-escaped cells as OISEC (OIS-escaped cells). OISEC lost the expression of p16 which plays an important role for cell cycle arrest for induction of senescence, but OISEC preserved the p16 expression machinery and exhibited senescence by the treatment with hydrogen peroxide (H2O2) as stress-induced premature senescence (SIPS). OISEC did not possess anchorage-independent growth potential, and functional disruption of p53 and Rb by SV40 early region encoding large T and small t antigens, induced the aneuploidy phenotype and colony-forming potential of OISEC together with the exhibition of in vivo tumor formation. Finally, we also found that the distinctive feature of OISEC is expression of transcription factors, Oct3/4, SOX2, and Nanog which is closely related to stem-like cell features. This study highlights the presence of a cell population which escaped from OIS, and this OISEC may transform into malignant cancer cells by the additional hits of several genes in vivo.

Original languageEnglish
Pages (from-to)878-884
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number4
Publication statusPublished - 2011 Jul 15
Externally publishedYes


  • Oncogene-induced senescence
  • P16
  • P53
  • Ras
  • Stem cell

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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