A new player in oncogenesis: AUF1/hnRNPD overexpression leads to tumorigenesis in transgenic mice

AUF1/heterogeneous nuclear ribonucleoprotein D (hnRNPD) binds to adenylate uridylate-rich elements contained in the 3' untranslated region of many short-lived mRNAs. This binding has been shown in vitro to control the stability of adenylate uridylate-rich element-containing mRNAs, including mRN...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2002-03, Vol.62 (5), p.1489-1495
Main Authors: Gouble, Agnàs, Grazide, Solàne, Meggetto, Fabienne, Mercier, Pascale, Delsol, Georges, Morello, Dominique
Format: Article
Language:English
Subjects:
Actins - genetics
Animals
Cyclin D1 - genetics
Granulocyte-Macrophage Colony-Stimulating Factor - genetics
Heterogeneous-Nuclear Ribonucleoprotein D
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Transgenic
RNA, Messenger - analysis
RNA-Binding Proteins - genetics
Sarcoma, Experimental - etiology
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Summary:AUF1/heterogeneous nuclear ribonucleoprotein D (hnRNPD) binds to adenylate uridylate-rich elements contained in the 3' untranslated region of many short-lived mRNAs. This binding has been shown in vitro to control the stability of adenylate uridylate-rich element-containing mRNAs, including mRNAs encoding proto-oncogenes, cytokines, or other signaling molecules. However, no studies have yet been undertaken to identify the mRNAs subject to AUF1-mediated regulation in vivo. The purpose of our study was to investigate the biological functions of AUF1. Thus, we derived transgenic (Tg) mice, which overexpress one isoform of AUF1, the p37(AUF1). Mice of the three Tg lines analyzed exhibit altered levels of expression of several target mRNAs, such as c-myc, c-jun, c-fos, granulocyte macrophage colony-stimulating factor, and tumor necrosis factor alpha. The Tg line with the highest amount of Tg p37(AUF1) protein developed sarcomas. The tumors strongly expressed AUF1 Tg protein and Cyclin D1. Taken together, our data show that: (a) AUF1 is a key regulatory factor of gene expression in vivo; and (b) the deregulation of this heterogeneous nuclear ribonucleoprotein leads to tumorigenesis.
ISSN:0008-5472