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GEO help: Mouse over screen elements for information. |
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| 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
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| 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
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| 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.
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| Contributor(s) |
Li Z, Orkin SH |
| Citation(s) |
18068631 |
| Submission date |
Oct 17, 2007 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Zhe Li |
| E-mail(s) |
li@bloodgroup.tch.harvard.edu
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| Phone |
617-919-2052
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| Organization name |
Children's Hospital Boston
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| Department |
Division of Hematology/Oncology
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| Lab |
Stuart Orkin's Lab
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| Street address |
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (51)
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| GSM238339 |
mammary tumor CR115, unsorted, replicate 1 |
| GSM238340 |
mammary tumor CR90-1, transplanted, unsorted |
| GSM238341 |
mammary tumor CR115, unsorted, replicate 2 |
| GSM238342 |
mammary tumor CR90-2, transplanted, unsorted |
| GSM238343 |
mammary tumor B459L, unsorted |
| GSM238344 |
mammary tumor B459U, unsorted |
| GSM238345 |
mammary tumor C117T1, unsorted |
| GSM238346 |
mammary tumor C117T3, unsorted |
| GSM238347 |
mammary tumor C117T5, unsorted |
| GSM238348 |
mammary tumor C117T6, unsorted |
| GSM238349 |
mammary tumor CR115-3, transplanted, unsorted |
| GSM238350 |
mammary tumor CR115-4, transplanted, unsorted |
| GSM238351 |
mammary tumor C231T1, unsorted |
| GSM238352 |
mammary tumor D481, unsorted |
| GSM238353 |
mammary tumor D14T1, unsorted |
| GSM238354 |
mammary tumor D14T2, unsorted |
| GSM238355 |
mammary tumor D206T1, unsorted |
| GSM238356 |
mammary tumor D206T2, unsorted |
| GSM238357 |
mammary tumor D279T1, unsorted |
| GSM238358 |
mammary tumor C393T1, unsorted |
| GSM238359 |
mammary tumor C395T2, unsorted |
| GSM238360 |
mammary tumor C395T5, unsorted |
| GSM238361 |
mammary tumor D9, unsorted |
| GSM238362 |
mammary tumor D203T1, unsorted |
| GSM238363 |
mammary tumor D254T1, unsorted |
| GSM238364 |
mammary tumor D254T2, unsorted |
| GSM238365 |
mammary tumor E93T1, unsorted |
| GSM238366 |
hyperplastic MECs G376H, sorted |
| GSM238367 |
hyperplastic MECs F493H, sorted |
| GSM238368 |
hyperplastic MECs G420H, sorted |
| GSM238369 |
mammary tumor F464T, sorted |
| GSM238370 |
mammary tumor F405T, sorted |
| GSM238371 |
mammary tumor E344T, sorted |
| GSM238372 |
mammary tumor D279T1P2, transplanted, sorted |
| GSM238373 |
mammary tumor D279T2P2, transplanted, sorted |
| GSM238374 |
mammary tumor E344T2P1, transplanted, sorted |
| GSM238375 |
mammary tumor F402TP2, transplanted, sorted |
| GSM238376 |
WT mammary gland G337, unsorted |
| GSM238377 |
WT mammary gland G360, unsorted |
| GSM238378 |
WT mammary gland G397, unsorted |
| GSM238379 |
mammary tumor G294T, sorted |
| GSM238380 |
WT mammary gland G340, unsorted |
| GSM238381 |
WT mammary gland H235, unsorted |
| GSM238382 |
hyperplastic MECs H464H, sorted |
| GSM238383 |
mammary tumor F433T1, sorted |
| GSM238384 |
mammary tumor F433T3, sorted |
| GSM238385 |
mammary tumor F433T4, sorted |
| GSM238386 |
mammary tumor F433T4P1, transplanted, sorted |
| GSM238387 |
mammary tumor G421T1, sorted |
| GSM238388 |
mammary tumor D396TP3, transplanted, sorted |
| GSM238389 |
mammary tumor D279T1P4, transplanted, sorted |
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| Relations |
| BioProject |
PRJNA103049 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE9355_RAW.tar |
250.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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