In vitro transformation of mesenchymal stem cells by oncogenic H-rasVal12.
Tissue stem cells may serve as progenitors for malignant tumors derived from the same tissue. Here, we report the establishment of immortalized human mesenchymal stem cells (ihMSC) and tested the feasibility of using ihMSC as presarcomatous cells. Immortalization was achieved by introducing the genes for human telomerase reverse transcriptase and Bmi1. ihMSC retained the potential for multi-directional differentiation of the original MSC. To transform ihMSC, we introduced an oncogenic H-ras(Val12) gene, and established the cell line ihMSC-ras. ihMSC-ras had the phenotype of fully transformed cells and retained adipogenic and chondrogenic, but not osteogenic, potential. Interestingly, ihMSC-ras demonstrated morphological features of autophagy, and inhibition of the ERK pathway suppressed the production of autophagosomes, indicating that ras/ERK signaling is responsible for the induction of autophagy. Thus ihMSC will serve as a material with which to analyze the tumorigenic and differentiation-modifying effects of candidate oncogenes involved in the development of sarcomas.
Shima
Yasuko
Y
Institute for Frontier Medical Sciences, Kyoto University, Shogoin, Kyoto 606-8507, Japan.
Okamoto
Takeshi
T
Aoyama
Tomoki
T
Yasura
Ko
K
Ishibe
Tatsuya
T
Nishijo
Koichi
K
Shibata
Kotaro R
KR
Kohno
Yoshiki
Y
Fukiage
Kenichi
K
Otsuka
Seiji
S
Uejima
Daisuke
D
Nakayama
Tomitaka
T
Nakamura
Takashi
T
Kiyono
Tohru
T
Toguchida
Junya
J
D018929:Cell Culture Techniques / Q000379:methods*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
D018631:ras Proteins