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Genome Biology

, 12:R77

First Online: 16 August 2011Received: 04 February 2011Revised: 29 April 2011Accepted: 16 August 2011

Abstract

BackgroundMicroRNAs miRNAs are small, non-coding, endogenous RNAs involved in regulating gene expression and protein translation. miRNA expression profiling of human breast cancers has identified miRNAs related to the clinical diversity of the disease and potentially provides novel diagnostic and prognostic tools for breast cancer therapy. In order to further understand the associations between oncogenic drivers and miRNA expression in sub-types of breast cancer, we performed miRNA expression profiling on mammary tumors from eight well-characterized genetically engineered mouse GEM models of human breast cancer, including MMTV-H-Ras -Her2-neu -c-Myc -PymT -Wnt1 and C31-SV40 T-t-antigen transgenic mice, BRCA1 ;p53;MMTV-cre knock-out mice and the p53 ;MMTV-cre transplant model.

ResultsmiRNA expression patterns classified mouse mammary tumors according to luminal or basal tumor subtypes. Many miRNAs found in luminal tumors are expressed during normal mammary development. miR-135b, miR-505 and miR-155 are expressed in both basal human and mouse mammary tumors and many basal-associated miRNAs have not been previously characterized. miRNAs associated with the initiating oncogenic event driving tumorigenesis were also identified. miR-10b -148a -150 -199a and -486 were only expressed in normal mammary epithelium and not tumors, suggesting that they may have tumor suppressor activities. Integrated miRNA and mRNA gene expression analyses greatly improved the identification of miRNA targets from potential targets identified in silico.

ConclusionsThis is the first large-scale miRNA gene expression study across a variety of relevant GEM models of human breast cancer demonstrating that miRNA expression is highly associated with mammary tumor lineage, differentiation and oncogenic pathways.

AbbreviationsEMTepithelial-to-mesenchymal transition

ERestrogen receptor

FACSfluorescence activated cell sorting

FDRfalse discovery rate

GEMgenetically engineered mouse

LTRlong terminal repeat

miRNAmicroRNA

MMTVmouse mammary tumor virus

PCRpolymerase chain reaction

PyMTpolyoma middle T antigen

RFPred fluorescence protein

RT-PCRreverse transcription PCR

UTRuntranslated region.

Electronic supplementary materialThe online version of this article doi:10.1186-gb-2011-12-8-r77 contains supplementary material, which is available to authorized users.

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Autor: Min Zhu - Ming Yi - Chang Hee Kim - Chuxia Deng - Yi Li - Daniel Medina - Robert M Stephens - Jeffrey E Green

Fuente: https://link.springer.com/







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