Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human HMLER breast cancer cells treated with paclitaxel and salinomycin-treated HMLER breast cancer cells


ABSTRACT: Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound, salinomycin, reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. Treatment of mice with salinomycin inhibits mammary tumor growth in vivo and induces increased epithelial differentiation of tumor cells. In addition, global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients. This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs Experiment Overall Design: Experimentally transformed HMLER breast cancer cells were treated in culture with either paclitaxel (10nM) or salinomycin (1uM) for one week. There were three biologic replicates for each treatment condition.

ORGANISM(S): Homo sapiens

SUBMITTER: Piyush Gupta 

PROVIDER: E-GEOD-17215 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Identification of selective inhibitors of cancer stem cells by high-throughput screening.

Gupta Piyush B PB   Onder Tamer T TT   Jiang Guozhi G   Tao Kai K   Kuperwasser Charlotte C   Weinberg Robert A RA   Lander Eric S ES  

Cell 20090813 4


Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound, salinomycin, reduces the proportion of CSCs by >100-fold relative to p  ...[more]

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