Sox2 expression in human stomach adenocarcinomas with gastric and gastric-and-intestinal-mixed phenotypes

Sox2 expression in human stomach adenocarcinomas with gastric and gastric-and-intestinal-mixed phenotypes
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DOI:
10.1111/j.1365-2559.2005.02170.x
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发表时间:
2005-06-01
期刊:
影响因子:
6.4
通讯作者:
Tatematsu, M
Tatematsu, M
中科院分区:
医学2区
文献类型:
--
作者:
Tsukamoto, T;Mizoshita, T;Tatematsu, M

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目的:除了肠道转录因子Cdx 1和Cdx 2的异位表达外,人类胃腺癌的胃和肠道表型的分子机制尚未详细阐明。我们已经报道,Sox 2,一个HMG盒胃转录因子,在正常胃粘膜中表达和下调肠化生。方法和结果:我们分析了Sox 2和其他分化标志物的mRNA水平在50例手术切除的胃腺癌,化学分类为胃(G),胃和肠(GI)混合,单纯肠(I),和空(N)型。Sox 2在G型和GI混合型腺癌中的表达与MUC5 AC和MUC6的表达一致,Cdx 1和Cdx 2在GI混合型和I型腺癌中的表达与MUC2和villin的表达沿着上调。在N型中,胃和肠的转录因子均被抑制。免疫组织化学证实了MUC5AC+病变中Sox 2的表达和Cdx 2与MUC2一起定位。胃腺癌细胞系KATOIII同时表达MUC5AC和Sox 2,但在Sox 2 + AGS细胞系中未检测到MUC5AC mRNA。结论:Sox 2可能与其他辅助因子协同作用,在维持胃癌和正常组织的胃表型中发挥重要作用。
Aims: Other than ectopic expression of intestinal transcription factors, Cdx1 and Cdx2, the molecular mechanisms underlying gastric and intestinal phenotypes of human stomach adenocarcinomas have yet to be clarified in detail. We have reported that Sox2, an HMG-box gastric transcription factor, is expressed in normal gastric mucosa and down-regulated in intestinal metaplasia.Methods and results: We analysed mRNA levels of Sox2 and other differentiation markers in 50 surgically resected stomach adenocarcinomas, immunohistochemically classified into gastric (G), gastric-and-intestinal (GI)-mixed, solely intestinal (I), and null (N) types. Sox2 was found to be transcribed in G and GI-mixed type adenocarcinomas in accordance with MUC5AC and MUC6 expression, while Cdx1 and Cdx2 were up-regulated in GI-mixed and I types along with the expression of MUC2 and villin. In the N type, both gastric and intestinal transcription factors were suppressed. Immunohistochemistry confirmed expression of Sox2 in MUC5AC+ lesions and Cdx2 localization together with MUC2. A stomach adenocarcinoma cell line, KATOIII, demonstrated both MUC5AC and Sox2, although MUC5AC mRNA was not detected in the Sox2+ AGS cell line.Conclusions: Sox2 may play an important role in maintaining a gastric phenotype in stomach cancers as well as in normal tissue, in cooperation with other cofactor(s).