Reference SummaryZhu M, Genome Biol 2011;12(8):R77

Title

Integrated miRNA and mRNA expression profiling of mouse mammary tumor models identifies miRNA signatures associated with mammary tumor lineage.

Authors

Zhu M; Yi M; Kim CH; Deng C; Li Y; Medina D; Stephens RM; Green JE

Journal

Genome Biol

Volume

12

Issue

8

Year

2011

Pages

R77

Abstract

BACKGROUND: MicroRNAs (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 C3(1)/SV40 T/t-antigen transgenic mice, BRCA1(fl/fl);p53(+/-);MMTV-cre knock-out mice and the p53(fl/fl);MMTV-cre transplant model. RESULTS: miRNA 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. CONCLUSIONS: This 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.

Links

J:216041 – Mouse Genome Informatics
21846369 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB Mammary gland normal tissue (control) Mammary gland

not applicable

STOCK Mammary gland normal tissue (control) Mammary gland

not applicable

BALB/c Mammary gland normal tissue (control) Mammary gland

not applicable

FVB/N-Tg(C3-1-TAg)cJeg Mammary gland tumor - basal Mammary gland

observed

STOCK Brca1tm2Cxd Tg(MMTV-cre)4Mam Trp53tm1Brd/+ Mammary gland tumor - basal Mammary gland

observed

FVB.Cg-Tg(MMTV-vHaras)#Pjo Mammary gland tumor - luminal Mammary gland

observed

FVB.Cg-Tg(MMTV-Erbb2)#Pjo Mammary gland tumor - luminal Mammary gland

observed

FVB.Cg-Tg(MMTV-Myc)#Led Mammary gland tumor - luminal Mammary gland

observed

FVB/N-Tg(MMTV-PyVT)634Mul Mammary gland tumor - luminal Mammary gland

observed

FVB.Cg-Tg(Wnt1)1Hev Mammary gland tumor - luminal Mammary gland

observed