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Nat Immunol. 2008 Apr;9(4):405-14. doi: 10.1038/ni1575. Epub 2008 Mar 9.

Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes.

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  • 1Immune Disease Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract

The genomic region encoding the miR-17-92 microRNA (miRNA) cluster is often amplified in lymphoma and other cancers, and cancer cells carrying this amplification have higher expression of miRNA in this cluster. Retroviral expression of miR-17-92 accelerates c-Myc-induced lymphoma development, but precisely how higher expression of miR-17-92 promotes lymphomagenesis remains unclear. Here we generated mice with higher expression of miR-17-92 in lymphocytes. These mice developed lymphoproliferative disease and autoimmunity and died prematurely. Lymphocytes from these mice showed more proliferation and less activation-induced cell death. The miR-17-92 miRNA suppressed expression of the tumor suppressor PTEN and the proapoptotic protein Bim. This mechanism probably contributed to the lymphoproliferative disease and autoimmunity of miR-17-92-transgenic mice and contributes to lymphoma development in patients with amplifications of the miR-17-92 coding region.

PMID:
18327259
[PubMed - indexed for MEDLINE]
PMCID:
PMC2533767
Free PMC Article
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