1. ¹Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
2. ²Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, PR China
3. ³Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
4. ⁴Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
5. ⁵Department of Urology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
6. ⁶Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
7. ⁷Department of Pathology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Correspondence: Dr Z Wang, Department of Urology, University of Pittsburgh, Shadyside Medical Center, Suite G40, 5200 Centre Avenue, Pittsburgh, PA 15232, USA. E-mail: wangz2@upmc.edu

⁸Current address: UCLA Immunogenetics Center, Los Angeles, CA 90095, USA.

Received 17 March 2007; Revised 13 August 2007; Accepted 13 August 2007; Published online 17 September 2007.

Abstract

Upregulated gene 19 (U19)/ELL-associated factor 2 (Eaf2) is a potential human tumor suppressor that exhibits frequent allelic loss and downregulation in high-grade prostate cancer. U19/Eaf2, along with its homolog Eaf1, has been reported to regulate transcriptional elongation via interaction with the eleven-nineteen lysine-rich leukemia (ELL) family of proteins. To further explore the tumor-suppressive effects of U19/Eaf2, we constructed and characterized a murine U19/Eaf2-knockout model. Homozygous or heterozygous deletion of U19/Eaf2 resulted in high rates of lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostate intraepithelial neoplasia. Within the mouse prostate, U19/Eaf2 deficiency enhanced cell proliferation and increased epithelial cell size. The knockout mice also exhibited cardiac cell hypertrophy. These data indicate a role for U19/Eaf2 in growth suppression and cell size control as well as argue for U19/Eaf2 as a novel tumor suppressor in multiple mouse tissues. The U19/Eaf2 knockout mouse also provides a unique animal model for three important cancers: lung adenocarcinoma, B-cell lymphoma and hepatocellular carcinoma.