Transcriptomics

Dataset Information

11

Transcription profiling of mouse mammary tumours developed in Wap-Cre;Etv6-NTRK3 mice


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. Given increasing relevance of chromosomal translocations in epithelial cancers, such mice serve as a paradigm for the study of their genetic pathogenesis and cellular origins, and generation of novel preclinical models. In this study, we generated microarray expression profiling data from both genetically marked, FACS-sorted tumor epithelial cells and from unfractionated mammary tumors and normal mammary glands. By using gene set enrichment analysis (GSEA) on these data, we have identified the AP1 transcriptional complex as the major downstream effector of the ETV6-NTRK3 signaling. Experiment Overall Design: Take the advantage of the Cre-lox system and a floxed lacZ reporter at the Rosa26 locus (Rosa-Stop-lacZ), we genetically marked mammary epithelial cells in which the conditional Etv6-NTRK3 knockin allele were turned on, and followed them to the hyperplasia and tumor stages. We then sorted lacZ+ hyperplastic mammary epithelial cells and lacZ+ tumor epithelial cells and collected their expression profiles by Affymetrix mouse whole genome MOE430.2 chips. We also collected expression profiles from unfractionated mammary tumors (unsorted tumors) derived from the same mouse model and mammary glands from normal mice.

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Mus musculus  

SUBMITTER: Zhe Li  

PROVIDER: E-GEOD-9355 | ArrayExpress | 2008-06-16

SECONDARY ACCESSION(S): GSE9355PRJNA103049

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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