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CITED1 Expression in Liver Development and Hepatoblastoma

Authors :
Andrew J. Murphy
Christian de Caestecker
Janene Pierce
Scott C. Boyle
Gregory D. Ayers
Zhiguo Zhao
Jaime M. Libes
Hernan Correa
Teagan Walter
Stacey S. Huppert
Alan O. Perantoni
Mark P. de Caestecker
Harold N. Lovvorn, III
Source :
Neoplasia: An International Journal for Oncology Research, Vol 14, Iss 12, Pp 1153-1163 (2012)
Publication Year :
2012
Publisher :
Elsevier, 2012.

Abstract

Hepatoblastoma, the most common pediatric liver cancer, consists of epithelial mixed embryonal/fetal (EMEF) and pure fetal histologic subtypes, with the latter exhibiting a more favorable prognosis. Few embryonal histology markers that yield insight into the biologic basis for this prognostic discrepancy exist. CBP/P-300 interacting transactivator 1 (CITED1), a transcriptional co-activator, is expressed in the self-renewing nephron progenitor population of the developing kidney and broadly in its malignant analog, Wilms tumor (WT). In this current study, CITED1 expression is detected in mouse embryonic liver initially on post-coitum day 10.5 (e10.5), begins to taper by e14.5, and is undetectable in e18.5 and adult livers. CITED1 expression is detected in regenerating murine hepatocytes following liver injury by partial hepatectomy and 3,5-diethoxycarbonyl-1,4-dihydrocollidine. Importantly, while CITED1 is undetectable in normal human adult livers, 36 of 41 (87.8%) hepatoblastoma specimens express CITED1, where it is enriched in EMEF specimens compared to specimens of pure fetal histology. CITED1 overexpression in Hep293TT human hepatoblastoma cells induces cellular proliferation and upregulates the Wnt inhibitors Kringle containing transmembrane protein 1 (KREMEN1) and CXXC finger protein 4 (CXXC4). CITED1 mRNA expression correlates with expression of CXXC4 and KREMEN1 in clinical hepatoblastoma specimens. These data show that CITED1 is expressed during a defined time course of liver development and is no longer expressed in the adult liver but is upregulated in regenerating hepatocytes following liver injury. Moreover, as in WT, this embryonic marker is reexpressed in hepatoblastoma and correlates with embryonal histology. These findings identify CITED1 as a novel marker of hepatic progenitor cells that is re-expressed following liver injury and in embryonic liver tumors.

Details

Language :
English
ISSN :
14765586 and 15228002
Volume :
14
Issue :
12
Database :
Directory of Open Access Journals
Journal :
Neoplasia: An International Journal for Oncology Research
Publication Type :
Academic Journal
Accession number :
edsdoj.0ca02d00ae4f45f28a4e012902e98800
Document Type :
article
Full Text :
https://doi.org/10.1593/neo.12958