Objectives: Transcription factor GATA-4 is expressed in early fetal liver and essential for organogenesis. It is also implicated in carcinogenesis in several endoderm-derived organs. Hepatoblastoma (HB), the most common malignant pediatric liver tumor, has features of fetal liver including extramedullary hematopoiesis. We investigated the expression of GATA-4 and its purported target gene erythropoietin (Epo) in liver tumors and the role of GATA-4 in HB pathogenesis.
Patients and Methods: Immunohistochemistry, Western blotting, and reverse transcription-polymerase chain reaction were used for liver samples from patients with HB or hepatocellular carcinoma. To further investigate the role of GATA-4 in pediatric liver tumors, we used adenoviral transfections of wild-type or dominant negative GATA-4 constructs in the human HB cell line, HUH6.
Results: We found abundant GATA-4 expression in both types of liver tumors in children, whereas it was absent in adult hepatocellular carcinoma. A close family member GATA-6 was expressed in a minority of childhood but not adult liver tumors. Epo, present in the fetal liver, was also expressed in childhood liver tumors. Moreover, cell line HUH6 was GATA-4 positive and produced Epo. We found that altering the amount of functional GATA-4 in HUH6 cells did not significantly affect either proliferation or apoptosis.
Conclusions: GATA-4 is abundant in pediatric liver tumors, but unraveling its exact role in these neoplasms requires further investigation.
*Pediatric Research Center, Children's Hospital
†Department of Pathology and Haartman Institute, HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki
‡Department of Pediatrics, University of Tampere and Tampere University Hospital, Tampere, Finland
§Department of Pediatrics and Developmental Biology, Washington University School of Medicine, St Louis, MO.
Address correspondence and reprint requests to Markku Heikinheimo, MD, PhD, Children's Hospital, University of Helsinki, PO Box 22 (Stenbäckinkatu 11), Helsinki 00014, Finland (e-mail: firstname.lastname@example.org).
Received 19 April, 2011
Accepted 30 June, 2011
Drs Soini and Haveri participated equally in this study.
This work was supported by grants from the Foundation for Paediatric Research, the Sigrid Juselius Foundation, and Helsinki University Central Hospital Research Funds.
The authors report no conflicts of interest.