title: Transcription factor GATA-4 is abundantly expressed in childhood but not in adult liver tumors.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Pediatric Research Center, Children's Hospital, Helsinki, Finland.
authors.forename: Tea
authors.initials: T
authors.lastname: Soini
authors.forename: Hanna
authors.initials: H
authors.lastname: Haveri
authors.forename: Jenni M
authors.initials: JM
authors.lastname: Elo
authors.forename: Marjut
authors.initials: M
authors.lastname: Kauppinen
authors.forename: Antti
authors.initials: A
authors.lastname: Kyrönlahti
authors.forename: Matti K
authors.initials: MK
authors.lastname: Salo
authors.forename: Jouko
authors.initials: J
authors.lastname: Lohi
authors.forename: Leif C
authors.initials: LC
authors.lastname: Andersson
authors.forename: David B
authors.initials: DB
authors.lastname: Wilson
authors.forename: Markku
authors.initials: M
authors.lastname: Heikinheimo
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002648:Child; D004921:Erythropoietin / Q000378:metabolism; D005333:Fetus / Q000378:metabolism*; D050991:GATA4 Transcription Factor / Q000378:metabolism*; D050993:GATA6 Transcription Factor / Q000378:metabolism; D018197:Hepatoblastoma / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D014162:Transfection
chemical_list: C554270:EPO protein, human; D050991:GATA4 Transcription Factor; D050993:GATA6 Transcription Factor; D004921:Erythropoietin