| First Author | Lee JS | Year | 2008 |
| Journal | Biochem Biophys Res Commun | Volume | 365 |
| Issue | 3 | Pages | 496-502 |
| PubMed ID | 18021740 | Mgi Jnum | J:130236 |
| Mgi Id | MGI:3771277 | Doi | 10.1016/j.bbrc.2007.11.005 |
| Citation | Lee JS, et al. (2008) Brain cancer stem-like cell genesis from p53-deficient mouse astrocytes by oncogenic Ras. Biochem Biophys Res Commun 365(3):496-502 |
| abstractText | Here, we show that H-ras(V12) causes the p53-knockout mouse astrocytes (p53-/- astrocytes) to be transformed into brain cancer stem-like cells. H-ras(V12) triggers the p53-/- astrocytes to express a Nestin and a Cd133, which are expressed in normal and cancer neural stem cells. H-ras(V12) also induces the formation of a single cell-derived neurosphere under neural stem cell culture conditions. Furthermore, H-ras(V12)-overexpressing p53-/- astrocytes (p53-/-ast-H-ras(V12)) 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. |
