Genetically engineered mouse models of prostate cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Parisotto M
PROVIDER: S-EPMC5528413 | biostudies-other | 2013 Apr
REPOSITORIES: biostudies-other
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Project description:Human breast cancer is a heterogeneous disease consisting of multiple molecular subtypes. Genetically engineered mouse models are a useful resource for studying mammary cancers in vivo under genetically controlled and immune competent conditions. Identifying murine models with conserved human tumor features will facilitate etiology determinations, highlight the effects of mutations on pathway activation, and should improve preclinical drug testing.Transcriptomic profiles of 27 murine models of mammary carcinoma and normal mammary tissue were determined using gene expression microarrays. Hierarchical clustering analysis identified 17 distinct murine subtypes. Cross-species analyses using three independent human breast cancer datasets identified eight murine classes that resemble specific human breast cancer subtypes. Multiple models were associated with human basal-like tumors including TgC3(1)-Tag, TgWAP-Myc and Trp53-/-. Interestingly, the TgWAPCre-Etv6 model mimicked the HER2-enriched subtype, a group of human tumors without a murine counterpart in previous comparative studies. Gene signature analysis identified hundreds of commonly expressed pathway signatures between linked mouse and human subtypes, highlighting potentially common genetic drivers of tumorigenesis.This study of murine models of breast carcinoma encompasses the largest comprehensive genomic dataset to date to identify human-to-mouse disease subtype counterparts. Our approach illustrates the value of comparisons between species to identify murine models that faithfully mimic the human condition and indicates that multiple genetically engineered mouse models are needed to represent the diversity of human breast cancers. The reported trans-species associations should guide model selection during preclinical study design to ensure appropriate representatives of human disease subtypes are used.
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Project description:3 Cell lines from Apc, p53 (AP) GEMMs were compared to 12 cell lines from Apc, Kras, p53 (AKP) GEMMs. Mouse 430 2.0 arrays were used to determine genomic expression differences between the two genotypes (AP and AKP). RNA was extracted from 3 AP and 10 AKP cell lines using the Qiagen RNEasy kit, and hybridized to individual Affymetrix mouse 430 2.0 chips as per manufacturer's instructions
2013-07-02 | E-GEOD-39557 | biostudies-arrayexpress
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