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Series GSE34479 Query DataSets for GSE34479
Status Public on Dec 17, 2011
Title Cooperativity of Rb, Brca1, and p53 and malignant breast cancer evolution
Organism Mus musculus
Experiment type Expression profiling by array
Third-party reanalysis
Summary Breast cancers that are “triple-negative” for the clinical markers ESR1, PGR, and HER2 typically belong to the Basal-like molecular subtype. Defective Rb, p53, and Brca1 pathways are each associated with triple-negative and Basal-like subtypes. Our mouse genetic studies demonstrate that the combined inactivation of Rb and p53 pathways is sufficient to suppress the physiological cell death of mammary involution. Furthermore, concomitant inactivation of all three pathways in mammary epithelium has an additive effect on tumor latency and predisposes highly penetrant, metastatic adenocarcinomas. The tumors are poorly differentiated and have histologic features that are common among human Brca1-mutated tumors, including heterogeneous morphology, metaplasia, and necrosis. Gene expression analyses demonstrate that the tumors share attributes of both Basal-like and Claudin-low signatures, two molecular subtypes encompassed by the broader, triple-negative class defined by clinical markers. These studies establish a unique animal model of aggressive forms of breast cancer for which there are no effective, targeted treatments. Rb, p53, and Brca1 are associated with inherited forms of cancer, but defects in these pathways are also found together in a subset of breast cancer patients without a family history of the disease. Simultaneous inactivation of all three pathways causes more aggressive disease than do pair-wise combinations, indicating that the pathways play non-overlapping roles in tumor prevention.
 
Overall design Gene expression analysis of mouse mammary tumors with perturbation of Rb family pathways, p53, and/or Brca1 are compared to other mouse model tumors (n=152)
 
Contributor(s) Karl S
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Submission date Dec 15, 2011
Last update date Dec 06, 2012
Contact name Karl Simin
E-mail(s) karl.simin@umassmed.edu
Organization name UMass Medical School
Street address 364 Plantation St.
City Worcester
State/province MA
ZIP/Postal code 01606
Country USA
 
Platforms (1)
GPL891 Agilent-011978 Mouse Microarray G4121A (Feature Number version)
Samples (22)
GSM849870 BALBc_WAP_T121_KS592_SIMIN
GSM849871 B6D2F1_WAP_T121_p53null_KS593_SIMIN
GSM849872 B6D2F1_WAP_T121_p53het_KS601_SIMIN
Relations
Affiliated with GSM80449
Affiliated with GSM238339
Affiliated with GSM238340
Affiliated with GSM238345
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Affiliated with GSM80426
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Affiliated with GSM80439
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Affiliated with GSM80441
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Affiliated with GSM80456
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Affiliated with GSM80458
Affiliated with GSM80459
Affiliated with GSM80433
BioProject PRJNA151343

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE34479_RAW.tar 20.0 Mb (http)(custom) TAR (of TXT)
GSE34479_rawfile_column_header.txt.gz 514 b (ftp)(http) TXT
Processed data included within Sample table
Processed data provided as supplementary file
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