Transcriptomics

Dataset Information

4

Transcription profiling of mouse model for ETV6-NTRK3 (EN) fusion oncoprotein expresson


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. We showed that forced expression of a dominant negative version of c-Jun (TAM67) in EN-transduced Eph4 mammary epithelial cells impairs their ability to form tumors in immunodeficient nude mice, thus provided validation that EN-initiated mammary tumorigenesis is largely mediated through the AP1 complex. Experiment Overall Design: To validate that EN-initiated mammary tumorigenesis is largely mediated through the AP1 complex, we generated EN-transduced Eph4 (EN-Eph4) mammary epithelial cells as well as EN-Eph4 cells co-expressing a dominant negative version of c-Jun (TAM67), and transplanted them into nude mice. We then isolated total RNAs from resulted tumors and collected their expression profiles using Affymetrix mouse MOE 430.2 chips.

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Mus musculus  

SUBMITTER: Zhe Li  

PROVIDER: E-GEOD-9353 | ArrayExpress | 2008-06-16

SECONDARY ACCESSION(S): GSE9353PRJNA103045

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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