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Series GSE9355 Query DataSets for GSE9355
Status Public on Dec 14, 2007
Title Microarray expression profiles of mammary tumors developed in Wap-Cre;Etv6-NTRK3 mice
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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.
Keywords: genetic modification, cell type comparison
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.
Contributor(s) Li Z, Orkin SH
Citation(s) 18068631
Submission date Oct 17, 2007
Last update date Feb 11, 2019
Contact name Zhe Li
Phone 617-919-2052
Organization name Children's Hospital Boston
Department Division of Hematology/Oncology
Lab Stuart Orkin's Lab
Street address
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (51)
GSM238339 mammary tumor CR115, unsorted, replicate 1
GSM238340 mammary tumor CR90-1, transplanted, unsorted
GSM238341 mammary tumor CR115, unsorted, replicate 2
BioProject PRJNA103049

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Supplementary file Size Download File type/resource
GSE9355_RAW.tar 250.2 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
Raw data provided as supplementary file

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