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 stemness 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.
Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aldehyde Dehydrogenase / metabolism
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Animals
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Antigens, Ly / metabolism*
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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Cell Line, Tumor
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Cell Proliferation* / drug effects
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Dose-Response Relationship, Drug
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Farnesyltranstransferase / antagonists & inhibitors
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Farnesyltranstransferase / metabolism
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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MAP Kinase Kinase Kinases / metabolism
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Membrane Proteins / metabolism*
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Methionine / analogs & derivatives
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Methionine / pharmacology
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Mice
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Mice, Inbred BALB C
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Neoplasm Invasiveness
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Neoplastic Stem Cells / drug effects
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Neoplastic Stem Cells / metabolism*
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Neoplastic Stem Cells / pathology
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Phosphorylation
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Protein Prenylation
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Signal Transduction
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Spheroids, Cellular
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ras Proteins / metabolism*
Substances
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Antigens, Ly
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Enzyme Inhibitors
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FTI 277
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Ly6a protein, mouse
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Membrane Proteins
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Methionine
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Aldehyde Dehydrogenase
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Farnesyltranstransferase
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MAP Kinase Kinase Kinases
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ras Proteins