title: U19/Eaf2 knockout causes lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostatic intraepithelial neoplasia.
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.
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: W
authors.initials: W
authors.lastname: Xiao
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: G
authors.initials: G
authors.lastname: Habermacher
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.forename: A-Y
authors.initials: AY
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Cai
authors.forename: J
authors.initials: J
authors.lastname: Hahn
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Pins
authors.forename: L
authors.initials: L
authors.lastname: Doglio
authors.forename: R
authors.initials: R
authors.lastname: Dhir
authors.forename: J
authors.initials: J
authors.lastname: Gingrich
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
mesh_terms: 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*
chemical_list: C472771:EAF2 protein, human; D014157:Transcription Factors; D013739:Testosterone