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CITED1 expression in liver development and hepatoblastoma
Andrew J Murphy1, Christian de Caestecker, Janene Pierce
1Department of Pediatric Surgery, Vanderbilt University Medical Center, Vanderbilt Children’s Hospital, Nashville, TN 37232-9780, USA. andrew.j.murphy@vanderbilt.edu
Neoplasia (New York, N.Y.)
|January 12, 2013
Summary
CBP/P-300 interacting transactivator 1 (CITED1) is an embryonic marker reexpressed in pediatric liver cancer (hepatoblastoma) and regenerating liver cells. This finding may explain prognostic differences in hepatoblastoma subtypes.
Area of Science:
- Developmental Biology
- Oncology
- Molecular Biology
Background:
- Hepatoblastoma is the most common pediatric liver cancer with varying prognoses based on histologic subtypes.
- Embryonal markers are needed to understand prognostic discrepancies in hepatoblastoma.
- CBP/P-300 interacting transactivator 1 (CITED1) is known to be expressed in developing kidney progenitor cells and Wilms tumor.
Purpose of the Study:
- To investigate the expression pattern of CITED1 in liver development, regeneration, and hepatoblastoma.
- To determine if CITED1 expression correlates with hepatoblastoma histology and prognosis.
Main Methods:
- CITED1 expression was analyzed in mouse embryonic and adult livers, regenerating hepatocytes, and human hepatoblastoma specimens.
- Overexpression studies in hepatoblastoma cells were performed to assess functional effects.
- Correlation analysis between CITED1, KREMEN1, and CXXC4 expression in clinical specimens was conducted.
Main Results:
- CITED1 is expressed in early mouse embryonic liver, decreases with development, and is absent in adult livers.
- CITED1 is reexpressed in regenerating hepatocytes after liver injury.
- 87.8% of hepatoblastoma specimens expressed CITED1, with higher levels in the embryonal mixed embryonal/fetal subtype.
- CITED1 overexpression promoted proliferation and upregulated Wnt inhibitors KREMEN1 and CXXC4 in hepatoblastoma cells.
- CITED1 mRNA expression correlated with CXXC4 and KREMEN1 in clinical samples.
Conclusions:
- CITED1 serves as a marker for hepatic progenitor cells during development.
- Reexpression of CITED1 in adult liver following injury and in hepatoblastoma suggests a role in regeneration and tumorigenesis.
- CITED1 may contribute to the distinct biological behavior and prognosis of hepatoblastoma subtypes.
