Ras activation contributes to the maintenance and expansion of Sca-1(pos) cells in a mouse model of breast cancer

Abstract

The cancer stem cell (CSC) hypothesis proposes that CSCs are the root of cancer and cause cancer metastasis and recurrence. In this study, we examined whether Ras signaling is associated with sternness of the CSCs population characterized by the stem cell antigen (Sca-1) phenotype in a 4T1 syngeneic mouse model of breast cancer. The Sca-1(pos) putative CSCs had high levels of activated Ras and phosphorylated MEK (p-MEK), compared with counterparts. The Ras farnesylation inhibitor (FTI-277) suppressed the maintenance and expansion of CSCs. Therefore, selective inhibition of Ras activation may be useful for stem-specific cancer therapy. (C) 2009 Elsevier Ireland Ltd. All rights reserved.