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Forkhead box protein A2, a pioneer factor for hepatogenesis, is involved in the expression of hepatic phenotype of alpha-fetoprotein-producing adenocarcinoma.
Yamamura, Nobuhisa; Fugo, Kazunori; Kishimoto, Takashi.
Afiliação
  • Yamamura N; Department of Molecular Pathology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
  • Fugo K; Department of Molecular Pathology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
  • Kishimoto T; Department of Molecular Pathology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. Electronic address: tkishi@faculty.chiba-u.jp.
Pathol Res Pract ; 213(9): 1082-1088, 2017 Sep.
Article em En | MEDLINE | ID: mdl-28778497
ABSTRACT
Alpha-fetoprotein (AFP)-producing adenocarcinoma is a high-malignant variant of adenocarcinoma with a hepatic or fetal-intestinal phenotype. The number of cases of AFP-producing adenocarcinomas is increasing, but the molecular mechanism underlying the aberrant production of AFP is unclear. Here we sought to assess the role of Forkhead box A (FoxA)2, which is a pioneer transcription factor in the differentiation of hepatoblasts. FoxA2 expression was investigated in five cases of AFP-producing gastric adenocarcinomas by immunohistochemistry, and all cases showed FoxA2 expression. Chromatin immunoprecipitation revealed the DNA binding of FoxA2 on the regulatory element of AFP gene in AFP-producing adenocarcinoma cells. The inhibition of FoxA2 expression with siRNA reduced the mRNA expression of liver-specific proteins, including AFP, albumin, and transferrin. The inhibition of FoxA2 also reduced the expressions of liver-enriched nuclear factors, i.e., hepatocyte nuclear factor (HNF) 4α and HNF6, although the expressions of HNF1α and HNF1ß were not affected. The same effect as FoxA2 knockdown in AFP producing adenocarcinoma cells was also observed in hepatocellular carcinoma cells. Our results suggest that FoxA2 plays a key role in the expression of hepatic phenotype of AFP-producing adenocarcinomas.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adenocarcinoma / Alfa-Fetoproteínas / Regulação Neoplásica da Expressão Gênica / Fator 3-beta Nuclear de Hepatócito Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adenocarcinoma / Alfa-Fetoproteínas / Regulação Neoplásica da Expressão Gênica / Fator 3-beta Nuclear de Hepatócito Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article