Activation of Notch signaling in human colon adenocarcinoma.
Activation of Notch signaling in human colon adenocarcinoma.
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DOI：
10.3892/ijo_00000112
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发表时间：
2008-12
影响因子：
5.2
通讯作者：
Egan SE
中科院分区：
文献类型：
--
作者：
Reedijk M;Odorcic S;Zhang H;Chetty R;Tennert C;Dickson BC;Lockwood G;Gallinger S;Egan SE
Notch和Wnt信号传导共同起作用以调节结肠祖细胞分裂和分化。在小鼠中的研究还表明，Notch信号传导是腺瘤形成所需的，以响应在人腺瘤性结肠息肉病的APCMin小鼠模型中发生的升高的Wnt途径信号传导。因此，我们使用原位杂交来分析Notch配体、受体和边缘基因以及Notch靶基因HES1在人结直肠癌（CRC）中的表达。在一小群肿瘤中，JAGGED配体、NOTCH 1、LFNG和HES 1的表达水平与隐窝中观察到的水平相似或更高。为了探索Notch信号传导可能在人类CRC中发挥定量作用的可能性，我们接下来分析了130个肿瘤中的HES1 mRNA表达，每个肿瘤都与结果数据相关。这些肿瘤中的绝大多数表达HES1，尽管水平不同。绝对表达水平与患者生存率无关。这些结果证实，JAG配体和NOTCH1以及Notch受体活化是人CRC的一致特征，并支持许多这些肿瘤（如APCMin小鼠）可能对抗Notch治疗方案有反应的观点。
Notch and Wnt signaling function together to regulate colonic progenitor cell division and differentiation. Studies in mice have also shown that Notch signaling is required for adenoma formation in response to elevated Wnt-pathway signaling that occurs in the APCMin mouse model of human adenomatous polyposis coli. We therefore used in situ hybridization to analyze expression of Notch ligands, receptors and fringe genes, as well as the Notch target gene, HES1, in human colorectal cancer (CRC). In a small cohort of tumors, JAGGED ligands, NOTCH1, LFNG and HES1 were expressed at levels similar to, or higher than, levels observed in the crypt. To explore the possibility that Notch signaling may play a quantitative role in human CRC we next analyzed HES1 mRNA expression in 130 tumors, each associated with outcome data. The vast majority of these tumors expressed HES1, although at varying levels. Absolute expression levels did not correlate with patient survival. These results establish that JAG ligands and NOTCH1, as well as Notch receptor activation are consistent features of human CRC and support the notion that many of these tumors, like the APCMin mouse, may respond to anti-Notch therapeutic regimes.
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影响因子：
11.2
作者：
Poynter, Jenny N.;Figueiredo, Jane C.;Le Marchand, Loic
通讯作者：
Le Marchand, Loic
DOI：
10.1196/annals.1339.048
发表时间：
2005-01-01
期刊：
TUMOR PROGRESSION AND THERAPEUTIC RESISTANCE
影响因子：
--
作者：
Leow, CC;Polakis, P;Gao, WQ
通讯作者：
Gao, WQ
影响因子：
3.2
作者：
Sander, GR;Powell, BC
通讯作者：
Powell, BC
影响因子：
11.2
作者：
Leow, CC;Romero, MS;Gao, WQ
通讯作者：
Gao, WQ
DOI：
10.1073/pnas.0707210104
发表时间：
2007-09-25
影响因子：
11.1
作者：
Kosinski, Cynthia;Li, Vivian S. W.;Chen, Xin
通讯作者：
Chen, Xin