TY - JOUR
T1 - A population of BJ fibroblasts escaped from Ras-induced senescence susceptible to transformation
AU - Kohsaka, Shinji
AU - Sasai, Ken
AU - Takahashi, Kenta
AU - Akagi, Tsuyoshi
AU - Tanino, Mishie
AU - Kimura, Taichi
AU - Nishihara, Hiroshi
AU - Tanaka, Shinya
N1 - Funding Information:
We thank Ms. Mami Sato and Dr. Masahisa Tsuji (Chromosome Science Labo Inc., Japan) for FISH analysis. Also, we thank Dr. Masataka Sugimoto (Research Institute, National Center for Geriatrics and Gerontology, Japan) for providing the plasmid. This study was supported in part by Grants-in-Aid from the Ministry of Education, Science, Culture, and Sports, Japan.
PY - 2011/7/15
Y1 - 2011/7/15
N2 - 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.
AB - 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.
KW - Oncogene-induced senescence
KW - P16
KW - P53
KW - Ras
KW - Stem cell
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U2 - 10.1016/j.bbrc.2011.06.082
DO - 10.1016/j.bbrc.2011.06.082
M3 - Article
C2 - 21703241
AN - SCOPUS:79960318553
SN - 0006-291X
VL - 410
SP - 878
EP - 884
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -
