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Transcription profiling by array of mammospheres derived from tumors of mice harboring Wnt/Met signaling mutations treated Wnt and MET pathway inhibitors

ABSTRACT: The combined activation of Wnt/ß-catenin and MET/HGF is required for mammary cancer stem cell (MaCSC) maintenance. We generated mammospheres derived from tumors of mice harboring Wnt/Met signaling mutations on which we performed microarray analysis to evaluate gene expression signatures controlled by Wnt and MET pathways. We used the gene expression profiles to dissect the role and the functions of these pathways in MaCSCs. We treated mammospheres with Wnt and MET pathway inhibitors (ICG-001 and PHA665752 respectively) alone or in combination. Samples treated with DMSO were used as vehicle control.

ORGANISM(S): Mus musculus

SUBMITTER: Jane Holland 

PROVIDER: E-GEOD-35899 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Combined Wnt/β-catenin, Met, and CXCL12/CXCR4 signals characterize basal breast cancer and predict disease outcome.

Holland Jane D JD   Györffy Balázs B   Vogel Regina R   Eckert Klaus K   Valenti Giovanni G   Fang Liang L   Lohneis Philipp P   Elezkurtaj Sefer S   Ziebold Ulrike U   Birchmeier Walter W  

Cell reports 20131127 5

Prognosis for patients with estrogen-receptor (ER)-negative basal breast cancer is poor, and chemotherapy is currently the best therapeutic option. We have generated a compound-mutant mouse model combining the activation of β-catenin and HGF (Wnt-Met signaling), which produced rapidly growing basal mammary gland tumors. We identified the chemokine system CXCL12/CXCR4 as a crucial driver of Wnt-Met tumors, given that compound-mutant mice also deficient in the CXCR4 gene were tumor resistant. Wnt-  ...[more]

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