U19/Eaf2 knockout causes lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostatic intraepithelial neoplasia.
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.
Xiao
W
W
Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Zhang
Q
Q
Habermacher
G
G
Yang
X
X
Zhang
A-Y
AY
Cai
X
X
Hahn
J
J
Liu
J
J
Pins
M
M
Doglio
L
L
Dhir
R
R
Gingrich
J
J
Wang
Z
Z
D000230:Adenocarcinoma / Q000235:genetics; D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D008113:Liver Neoplasms / Q000235:genetics; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics*; D013739:Testosterone / Q000097:blood; D014157:Transcription Factors / Q000502:physiology*
C472771:EAF2 protein, human; D014157:Transcription Factors; D013739:Testosterone