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Transcription factor GATA-4 is abundantly expressed in childhood but not in adult liver tumors.

AbstractOBJECTIVES:
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.
AuthorsTea Soini, Hanna Haveri, Jenni M Elo, Marjut Kauppinen, Antti Kyrönlahti, Matti K Salo, Jouko Lohi, Leif C Andersson, David B Wilson, Markku Heikinheimo
JournalJournal of pediatric gastroenterology and nutrition (J Pediatr Gastroenterol Nutr) Vol. 54 Issue 1 Pg. 101-8 (Jan 2012) ISSN: 1536-4801 [Electronic] United States
PMID21788913 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • EPO protein, human
  • GATA4 Transcription Factor
  • GATA6 Transcription Factor
  • Erythropoietin
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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