Abstract | 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.
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Authors | Tea Soini, Hanna Haveri, Jenni M Elo, Marjut Kauppinen, Antti Kyrönlahti, Matti K Salo, Jouko Lohi, Leif C Andersson, David B Wilson, Markku Heikinheimo |
Journal | Journal of pediatric gastroenterology and nutrition
(J Pediatr Gastroenterol Nutr)
Vol. 54
Issue 1
Pg. 101-8
(Jan 2012)
ISSN: 1536-4801 [Electronic] United States |
PMID | 21788913
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- EPO protein, human
- GATA4 Transcription Factor
- GATA6 Transcription Factor
- Erythropoietin
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Topics |
- Adenoviridae
(genetics)
- Adult
- Animals
- Apoptosis
- Carcinoma, Hepatocellular
(metabolism)
- Cell Line, Tumor
- Cell Proliferation
- Child
- Erythropoietin
(metabolism)
- Fetus
(metabolism)
- GATA4 Transcription Factor
(metabolism)
- GATA6 Transcription Factor
(metabolism)
- Hepatoblastoma
(metabolism)
- Humans
- Liver
(metabolism)
- Liver Neoplasms
(metabolism)
- Mice
- Mice, Inbred C57BL
- Transfection
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