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A population of BJ fibroblasts escaped from Ras-induced senescence susceptible to transformation
Title: | A population of BJ fibroblasts escaped from Ras-induced senescence susceptible to transformation |
Authors: | Kohsaka, Shinji Browse this author | Sasai, Ken Browse this author | Takahashi, Kenta Browse this author | Akagi, Tsuyoshi Browse this author | Tanino, Mishie Browse this author | Kimura, Taichi Browse this author | Nishihara, Hiroshi Browse this author | Tanaka, Shinya Browse this author |
Keywords: | Oncogene-induced senescence | Ras | p16 | p53 | Stem cell |
Issue Date: | 15-Jul-2011 |
Publisher: | Elsevier |
Journal Title: | Biochemical and Biophysical Research Communications |
Volume: | 410 |
Issue: | 4 |
Start Page: | 878 |
End Page: | 884 |
Publisher DOI: | 10.1016/j.bbrc.2011.06.082 |
PMID: | 21703241 |
Abstract: | 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. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/46956 |
Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 高阪 真路
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