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

  1. Author:
    Zhu, M.
    Yi, M.
    Kim, C. H.
    Deng, C. X.
    Li, Y.
    Medina, D.
    Stephens, R. M.
    Green, J. E.

  2. Author Address

    [Zhu, M; Green, JE] NCI, Transgen Oncogenesis & Genom Sect, Lab Cell Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. [Yi, M; Stephens, RM] NCI, Adv Biomed Comp Ctr, FCRDC, Frederick, MD 21702 USA. [Kim, CH] NCI, Lab Mol Technol, FCRDC, Frederick, MD 21702 USA. [Deng, CX] NIDDK, Mammalian Genet Sect, NIH, Bethesda, MD 20892 USA. [Li, Y] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. [Medina, D] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.;Green, JE (reprint author), NCI, Transgen Oncogenesis & Genom Sect, Lab Cell Biol & Genet, Ctr Canc Res, Bldg 37,Room 4054,37 Convent Dr, Bethesda, MD 20892 USA;jegreen@nih.gov
    1. Year: 2011
    2. Date: Aug 16
  2. Journal: Genome Biology
    1. 12
    2. 8
    3. Pages: 16
  4. Type of Article: Article
  5. Article Number: R77
  6. ISSN: 1474-760X
  1. 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 knockout 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.

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External Sources

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  2. DOI: 10.1186/gb-2011-12-8-r77
  3. View record in Web of Science®
  4. WOS: 000296649500007

Library Notes

  1. Fiscal Year: FY2010-2011
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