| Autor: |
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 |
| Předmět: |
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| Zdroj: |
Gastric Cancer; Jan2023, Vol. 26 Issue 1, p44-54, 11p |
| Abstrakt: |
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] |
| Databáze: |
Complementary Index |
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