In vitro transformation of mesenchymal stem cells by oncogenic H-rasVal12
| Autor: | Tatsuya Ishibe, Takashi Nakamura, Kenichi Fukiage, Junya Toguchida, Ko Yasura, Seiji Otsuka, Yasuko Shima, Daisuke Uejima, Tohru Kiyono, Koichi Nishijo, Takeshi Okamoto, Tomitaka Nakayama, Tomoki Aoyama, Yoshiki Kohno, Kotaro R. Shibata |
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| Rok vydání: | 2006 |
| Předmět: |
Cellular differentiation
Mesenchymal stem cell Biophysics Cell Culture Techniques Mesenchymal Stem Cells Sarcoma Cell Biology Biology Biochemistry Cell biology Endothelial stem cell Cell Transformation Neoplastic Genes ras Cancer stem cell ras Proteins Humans Telomerase reverse transcriptase Stem cell Progenitor cell Molecular Biology Cells Cultured Adult stem cell |
| Zdroj: | Biochemical and biophysical research communications. 353(1) |
| ISSN: | 0006-291X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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