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[Cancer Research 62, 1489-1495, March 1, 2002]
© 2002 American Association for Cancer Research

Molecular Biology and Genetics

A New Player in Oncogenesis: AUF1/hnRNPD Overexpression Leads to Tumorigenesis in Transgenic Mice1

Agnàs Gouble, Solàne Grazide, Fabienne Meggetto, Pascale Mercier, Georges Delsol and Dominique Morello2

Centre de Biologie du Développement, CNRS-UMR5547, Université Paul Sabatier, Bâtiment 4R3, 31062 Toulouse, Cedex 4 [A. G., D. M.]; Institut Claudius Régaud, INSERM E9910, 20 rue du Pont Saint Pierre, 31052 Toulouse [S. G.]; UPR CNRS 2163 and Service d’Anatomie et de Cytologie Pathologiques, Hôpital Purpan, 31059 Toulouse, Cedex [F. M., G. D.]; Institut de Pharmacologie et de Biologie Structurale, UMR 5089, 31062 Toulouse, Cedex [P. M.], France

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 p37AUF1. 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 p37AUF1 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.




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