Transcriptomics

Dataset Information

14

Transcription profiling by array of mammary gland tumors from FVB mice mutant for E2F


ABSTRACT: Advances in genomic signatures have begun to dissect breast cancer heterogeneity, and application of these signatures will allow the prediction of which pathways are important in tumor development. Here we used genomic signatures to predict involvement of specific E2F transcription factors in Myc-induced tumors. We genetically tested this prediction by interbreeding Myc transgenics with mice lacking various activator E2F alleles. Tumor latency decreased in the E2F1 mutant background and significantly increased in both the E2F2 and E2F3 mutants. Investigating the mechanism behind these changes revealed a reduction in apoptosis in the E2F1 knockout strain. E2F2 and E2F3 mutant backgrounds alleviated Myc effects on the mammary gland, reducing the susceptible tumor target population. Gene expression data from tumors revealed that the E2F2 knockout background resulted in fewer tumors with EMT, corresponding with a reduction in probability of Ras activation. In human breast cancer we found that a low probability of E2F2 pathway activation was associated with increased relapse-free survival time. Together these data illustrate the predictive utility of genomic signatures in deciphering the heterogeneity within breast cancer and illustrate the unique genetic requirements for individual E2Fs in mediating tumorigenesis in both mouse models and human breast cancer. MMTV-Myc tumors were generated in an E2F wild-type, E2F1 null, E2F2 null and E2F3 heterozygous background. When the primary tumor reached the endpoint, the tumors were flash frozen. 20 tumors from each genotype were selected for microarray analysis.

REANALYSED by: E-GEOD-24594

ORGANISM(S): Mus musculus  

SUBMITTER: Inez Yuwanita   Eran Andrechek  Eran R Andrechek  Kenichiro Fujiwara 

PROVIDER: E-GEOD-24594 | ArrayExpress | 2011-12-29

SECONDARY ACCESSION(S): GSE24594PRJNA132381

REPOSITORIES: GEO, ArrayExpress

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Publications

Prediction and genetic demonstration of a role for activator E2Fs in Myc-induced tumors.

Fujiwara Kenichiro K   Yuwanita Inez I   Hollern Daniel P DP   Andrechek Eran R ER  

Cancer research 20110118 5


Advances in genomic signatures have begun to dissect breast cancer heterogeneity and application of these signatures will allow the prediction of which pathways are important in tumor development. Here we used genomic signatures to predict involvement of specific E2F transcription factors in Myc-induced tumors. We genetically tested this prediction by interbreeding Myc transgenics with mice lacking various activator E2F alleles. Tumor latency decreased in the E2F1 mutant background and significa  ...[more]

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