Department of Biochemistry and Biophysics, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania.
Med Oncol. 2013 Mar;30(1):438. doi: 10.1007/s12032-012-0438-y. Epub 2013 Jan 13.
Notch signaling pathway is a highly conserved developmental pathway, which plays an important role in the regulation of cellular proliferation, differentiation and apoptosis. Deregulation of Notch pathway has been connected with the carcinogenesis in a variety of cancers. In this study, we investigated the expression of Notch receptors (NOTCH1, NOTCH2, NOTCH3 and NOTCH4), ligands (JAG1, JAG2 and DLL1) and target gene HES1. Fifty paired samples of endometrial cancer and adjacent nontumor endometrial tissue from endometrial cancer patients were analyzed by quantitative PCR. The mRNA levels of all investigated molecules were lower in endometrial cancer compared to adjacent nontumor tissue. The expression of NOTCH1, NOTCH4 and DLL1 in IB stage adenocarcinoma was significantly lower (P < 0.05) than the expression in IA stage adenocarcinoma. Significant correlations were found between mRNA expression levels of Notch target gene HES1 and several Notch signaling molecules: NOTCH1, NOTCH3, DLL1 (P < 0.001) and NOTCH2, JAG2 (P < 0.05). This supports the notion that Notch pathway can function as tumor suppressor in human endometrial cancer.
Notch 信号通路是一条高度保守的发育途径，在调节细胞增殖、分化和凋亡方面发挥着重要作用。 Notch 通路的失调与多种癌症的癌变有关。在这项研究中，我们研究了 Notch 受体（NOTCH1、NOTCH2、NOTCH3 和 NOTCH4）、配体（JAG1、JAG2 和 DLL1）和靶基因 HES1 的表达。通过定量 PCR 分析了 50 对子宫内膜癌患者的子宫内膜癌和相邻非肿瘤子宫内膜组织的配对样本。与相邻非肿瘤组织相比，所有研究分子在子宫内膜癌中的 mRNA 水平均较低。IB 期腺癌中 NOTCH1、NOTCH4 和 DLL1 的表达明显低于 IA 期腺癌（P<0.05）。 Notch 靶基因 HES1 的 mRNA 表达水平与 Notch 信号通路的几个分子之间存在显著相关性：NOTCH1、NOTCH3、DLL1（P<0.001）和 NOTCH2、JAG2（P<0.05）。这支持了 Notch 通路在人子宫内膜癌中可能作为肿瘤抑制因子发挥作用的观点。
