Brain cancer stem-like cell genesis from p53-deficient mouse astrocytes by oncogenic Ras

Joong Seob Lee, Jung Eun Gil, Jong Hoon Kim, Tae Kyung Kim, Xun Jin, Se Yeong Oh, Young Woo Sohn, Hye Min Jeon, Hyo Jung Park, Jong Whi Park, Yong Jae Shin, Yong Gu Chung, Jang Bo Lee, Seungkwon You, Hyunggee Kim

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Here, we show that H-rasV12 causes the p53-knockout mouse astrocytes (p53-/- astrocytes) to be transformed into brain cancer stem-like cells. H-rasV12 triggers the p53-/- astrocytes to express a Nestin and a Cd133, which are expressed in normal and cancer neural stem cells. H-rasV12 also induces the formation of a single cell-derived neurosphere under neural stem cell culture conditions. Furthermore, H-rasV12-overexpressing p53-/- astrocytes (p53-/-ast-H-rasV12) possess an in vitro self-renewal capacity, and are aberrantly differentiated into Tuj1-positve neurons both in vitro and in vivo. Amongst a variety of Ras-mediated canonical signaling pathways, we demonstrated that the MEK/ERK signaling pathway is responsible for neurosphere formation in p53-deficient astrocytes, whereas the PI3K/AKT signaling pathway is involved in oncogenic transformation in these cells. These findings suggest that the activation of Ras signaling pathways promotes the generation of brain cancer stem-like cells from p53-deficient mouse astrocytes by changing cell fate and transforming cell properties.

Original languageEnglish
Pages (from-to)496-502
Number of pages7
JournalBiochemical and biophysical research communications
Volume365
Issue number3
DOIs
Publication statusPublished - 2008 Jan 18

Keywords

  • Astrocyte
  • Brain cancer stem-like cells
  • Cell differentiation fate
  • Glioma
  • H-ras
  • p53

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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