Down-regulation of a gastric transcription factor, Sox2, and ectopic expression of intestinal homeobox genes, Cdx1 and Cdx2: Inverse correlation during progression from gastric/intestinal-mixed to complete intestinal metaplasia

Tetsuya Tsukamoto, Kenichi Inada, Harunari Tanaka, Tsutomu Mizoshita, Mami Mihara, Toshikazu Ushijima, Yoshitaka Yamamura, Shigeo Nakamura, Masae Tatematsu

研究成果: Article査読

125 被引用数 (Scopus)

抄録

Purpose: The molecular mechanisms underlying the development of intestinal metaplasia (IM) of the human stomach have yet to be clarified in detail. Besides ectopic expression of intestinal transcription factors, Cdx1 and Cdx2, little information is available regarding other regulatory factors. Hence, we here analyzed Sox2, a human homolog of a chicken gastric transcription factor, with reference to our new classification for gastric/intestinal (GI)-mixed type IM. Methods: Twenty specimens of surgically resected antral mucosa were subjected to a gland isolation technique. Isolated glands were classified into gastric (G), GI-mixed, and solely intestinal (I) types according to Alcian blue and paradoxical concanavalin A staining and were quantified for mRNA levels of gastrointestinal markers. Results: MUC5AC and MUC6 transcripts decreased with the progression of IM, while MUC2 and villin-1 were inversely correlated. Sox2 showed a gradual decrease from G, through GI, to the I type (G vs GI and GI vs I, P < 0.01 and P < 0.005, respectively). On the other hand, Cdxl (G vs GI and GI vs I, P < 0.0001 and P = 0.337, respectively) and Cdx2 (G vs GI and GI vs I, P < 0.0001 and P < 0.05, respectively) appeared in IM. Immunohistochemical study confirmed decreased expression of Sox2 and ectopic emergence of Cdx2 protein in IM glands. Conclusion: Down-regulation of Sox2, besides ectopic expression of Cdx genes, may be important factors for the development of IM.

本文言語English
ページ(範囲)135-145
ページ数11
ジャーナルJournal of Cancer Research and Clinical Oncology
130
3
DOI
出版ステータスPublished - 03-2004
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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