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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1536-1544 |
| Number of pages | 9 |
| Journal | Oncogene |
| Volume | 27 |
| Issue number | 11 |
| DOIs | |
| State | Published - Mar 6 2008 |
Funding
We thank Moira Hitchens for editing, Katherine Rundell for providing reagents, Minh Nguyen for critical reading, Katherine O’Malley and Fei Su for technical su pport and members of the Wang lab for extensive discussion. This work was supported in part by NIH R01 DK51193, NIH R01 CA120386, and NIH P50 CA90386 Prostate Cancer SPORE.
Keywords
- B-cell lymphoma
- Hepatocellular carcinoma
- Lung adenocarcinoma
- Prostate cancer
- Tumor suppressor
- U19/Eaf2
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research
