A role for Hath1, a bHLH transcription factor, in colon adenocarcinoma
A role for Hath1, a bHLH transcription factor, in colon adenocarcinoma
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DOI：
10.1196/annals.1339.048
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Gao, WQ
中科院分区：
文献类型：
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作者：
Leow, CC;Polakis, P;Gao, WQ
结肠腺癌是结肠癌的主要类型，临床标本中常可观察到杯状细胞显著减少或丢失。缺少Notch信号通路下游的bHLH转录因子Math1的小鼠表明Math1对于包括杯状细胞在内的肠道分泌细胞的细胞命运是必需的。检测人类Math1的同源基因Hath1在多个结肠癌样本和结肠癌细胞系中的表达显示，Hath1在结肠癌样本和结肠癌细胞系中的表达显著降低。Hath1在HT29结肠癌细胞系中的表达在体内外均能显著抑制HT29结肠癌细胞系的增殖和非贴壁生长。在分子水平上，Hath1可能调节MUC2的表达，MUC2是一种由杯状细胞分泌的粘蛋白，Hath1也可能是一个新的因子，通常由于Wnt信号通路的激活而受到抑制，该信号通路显然与结肠肿瘤的发生有关。
A significant reduction or loss of goblet cells is often observed in clinical samples of colon adenocarcinomas, which is the predominant form of colon carcinoma. Mice lacking Math1, a bHLH transcription factor downstream of the Notch signaling pathway, demonstrates that Math1 is necessary for cell fate determination of the intestinal secretory cells, including goblet cells. Examination of Hath1, the human orthologue of Math1, expression in multiple colon tumor samples and colon cancer cell lines reveals a dramatic decrease in Hath1 expression in colon tumor samples and colon cancer cell lines. Hath1 expression in the HT29 colon cancer cell line can significantly inhibit its proliferation and anchorage-independent growth both in vitro and in vivo. At the molecular level, Hath1 may regulate the expression of MUC2, a mucin secreted by goblet cells, and Hath1 may also be a novel factor normally repressed as a consequence of activation of the Wnt signaling pathway, which has been clearly implicated in colon tumorigenesis.