Transcriptomics

Dataset Information

31

The effect of dominant negative c-Jun, TAM67, on tumorigenesis of ETV6-NTRK3 transduced Eph4 cells


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. Keywords: genetic modification, cell type comparison 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.

REANALYSED by: GSE119128

INSTRUMENT(S): [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array

ORGANISM(S): Mus musculus  

SUBMITTER: Zhe Li   

PROVIDER: GSE9353 | GEO | 2007-12-14

SECONDARY ACCESSION(S): PRJNA103045

REPOSITORIES: GEO

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