Transcriptomics

Dataset Information

4

Transcription profiling of mouse model that recapitulates the ETV6-NTRK3 fusion oncoprotein the product of the t(12;15)(p13;q25) translocation characteristic of human secretory breast carcinoma


ABSTRACT: We report a mouse model that recapitulates expression of the ETV6-NTRK3 (EN) fusion oncoprotein, the product of the t(12;15)(p13;q25) translocation characteristic of human secretory breast carcinoma. Activation of EN expression in mammary tissues by Whey acidic protein (Wap) promoter-driven Cre leads to fully penetrant, multifocal malignant breast cancer with short latency. We provide genetic evidence that committed bipotent or CD61+ luminal alveolar progenitors, are targets of tumorigenesis. Furthermore, EN transforms these otherwise transient progenitors through activation of the AP1 complex. To study the initial effects of ETV6-NTRK3 (EN) mediated transformation, we retrovirally transduced NIH 3T3 cells and generated microarray expression profiling data of EN transduced 3T3 cells as well as control 3T3 cells. Using gene set enrichment analysis (GSEA), we identified a signature involving the AP1 transcriptional complex in EN transduced 3T3 cells. Experiment Overall Design: We retrovirally transduced NIH 3T3 cells with either EN, or controls (either the empty vector or a kinase-dead version of EN with a mutation at the kinase domain of NTRK3). We then prepared total RNAs from these cells and collected microarray expression profiling data from them using Affymetrix mouse MOE430A chips.

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Mus musculus  

SUBMITTER: Zhe Li  

PROVIDER: E-GEOD-9354 | ArrayExpress | 2008-06-16

SECONDARY ACCESSION(S): GSE9354PRJNA103047

REPOSITORIES: GEO, ArrayExpress

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Publications

ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex.

Li Zhe Z   Tognon Cristina E CE   Godinho Frank J FJ   Yasaitis Laura L   Hock Hanno H   Herschkowitz Jason I JI   Lannon Chris L CL   Cho Eunah E   Kim Seong-Jin SJ   Bronson Roderick T RT   Perou Charles M CM   Sorensen Poul H PH   Orkin Stuart H SH  

Cancer cell 20071201 6


To better understand the cellular origin of breast cancer, we developed a mouse model that recapitulates expression of the ETV6-NTRK3 (EN) fusion oncoprotein, the product of the t(12;15)(p13;q25) translocation characteristic of human secretory breast carcinoma. Activation of EN expression in mammary tissues by Wap-Cre leads to fully penetrant, multifocal malignant breast cancer with short latency. We provide genetic evidence that, in nulliparous Wap-Cre;EN females, committed alveolar bipotent or  ...[more]

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