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.
In: Gastric Cancer, Jg. 26 (2023), Heft 1, S. 44-54
academicJournal
Zugriff:
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. [ABSTRACT FROM AUTHOR]
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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.
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Autor/in / Beteiligte Person: | 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 |
Zeitschrift: | Gastric Cancer, Jg. 26 (2023), Heft 1, S. 44-54 |
Veröffentlichung: | 2023 |
Medientyp: | academicJournal |
ISSN: | 1436-3291 (print) |
DOI: | 10.1007/s10120-022-01334-5 |
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