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Transcriptome analysis reveals the essential role of NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) in gastric adenocarcinoma of fundic-gland type.
Fukagawa, Kazushi; Takahashi, Yu; Yamamichi, Nobutake; Kageyama-Yahara, Natsuko; Sakaguchi, Yoshiki; Obata, Miho; Cho, Rina; Sakuma, Nobuyuki; Nagao, Sayaka; Miura, Yuko; Tamura, Naoki; Ohki, Daisuke; Mizutani, Hiroya; Yakabi, Seiichi; Minatsuki, Chihiro; Niimi, Keiko; Tsuji, Yosuke; Yamamichi, Mitsue; Shigi, Narumi; Tomida, Shuta; Abe, Hiroyuki; Ushiku, Tetsuo; Koike, Kazuhiko; Fujishiro, Mitsuhiro.
Afiliación
  • Fukagawa K; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Takahashi Y; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan. yutakahashi-tky@umin.ac.jp.
  • Yamamichi N; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Kageyama-Yahara N; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Sakaguchi Y; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Obata M; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Cho R; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Sakuma N; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Nagao S; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Miura Y; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Tamura N; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Ohki D; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Mizutani H; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Yakabi S; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Minatsuki C; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Niimi K; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Tsuji Y; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Yamamichi M; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Shigi N; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Tomida S; Center for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, Okayama, Japan.
  • Abe H; Department of Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan.
  • Ushiku T; Department of Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan.
  • Koike K; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • Fujishiro M; Kanto Central Hospital of the Mutual Aid Association of Public School Teachers, Setagaya-Ku, Tokyo, Japan.
Gastric Cancer ; 26(1): 44-54, 2023 01.
Article en En | MEDLINE | ID: mdl-36094595
BACKGROUND: Gastric adenocarcinoma of fundic-gland type (GA-FG) is a gastric malignancy with little relation to Helicobacter pylori. Clinical characteristics of GA-FG have been established, but molecular mechanisms leading to tumorigenesis have not yet been elucidated. METHODS: We subjected three GA-FG tumors-normal mucosa pairs to microarray analysis. Network analysis was performed for the top 30 up-regulated gene transcripts, followed by immunohistochemical staining to confirm the gene expression analysis results. AGS and NUGC4 cells were transfected with the gene-encoding NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) to evaluate transcriptional changes in its target genes. RESULTS: Comprehensive gene expression analysis identified 1410 up-regulated and 1395 down-regulated gene probes with ≥ two-fold difference in expression. Among the top 30 up-regulated genes in GA-FG, we identified transcription factor NKX2-1/TTF-1, a master regulator of lung/thyroid differentiation, together with surfactant protein B (SFTPB), SFTPC, and secretoglobin family 3A member 2(SCGB3A2), which are regulated by NKX2-1/TTF-1. Immunohistochemical analysis of 16 GA-FG specimens demonstrated significantly higher NKX2-1/TTF-1 and SFTPB levels, as compared to that in adjacent normal mucosa (P < 0.05), while SCGB3A2 levels did not differ (P = 0.341). Transduction of NKX2-1/TTF-1 into AGS and NUGC4 cells induced transactivation of SFTPB and SFTPC, indicating that NKX2-1/TTF-1 can function as normally in gastric cells as it can in the lung cells. CONCLUSIONS: Our first transcriptome analysis of GA-FG indicates significant expression of NKX2-1/TTF1 in GA-FG. Immunohistochemistry and cell biology show ectopic expression and normal transactivation ability of NKX2-1/TTF-1, suggesting that it plays an essential role in GA-FG development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Adenocarcinoma Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Gastric Cancer Asunto de la revista: GASTROENTEROLOGIA / NEOPLASIAS Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Japón
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Adenocarcinoma Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Gastric Cancer Asunto de la revista: GASTROENTEROLOGIA / NEOPLASIAS Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Japón