Article abstract
Nature Immunology 9, 405 - 414 (2008)
Published online: 9 March 2008 | doi:10.1038/ni1575
Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes
Changchun Xiao1,3, Lakshmi Srinivasan1,3, Dinis Pedro Calado1, Heide Christine Patterson1, Baochun Zhang1, Jing Wang1, Joel M Henderson2, Jeffrey L Kutok2 & Klaus Rajewsky1
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.
- Immune Disease Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
- Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
- These authors contributed equally to this work.
Correspondence to: Klaus Rajewsky1 e-mail: rajewsky@cbr.med.harvard.edu