Expression of DCC and netrin-1 in normal human endometrium and its implication in endometrial carcinogenesis
Expression of DCC and netrin-1 in normal human endometrium and its implication in endometrial carcinogenesis
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DOI：
10.1016/j.ygyno.2004.07.050
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发表时间：
2004-11-01
影响因子：
4.7
通讯作者：
Wake, N
中科院分区：
文献类型：
--
作者：
Kato, HD;Kondoh, H;Wake, N
客观的。尽管 DCC 被认为是一种候选肿瘤抑制因子，但它在子宫内膜和致癌过程中所发挥的作用仍不清楚。为了更清楚地定义这些作用，我们检查了正常子宫内膜和子宫内膜癌中 DCC 及其配体 netrin-1 的表达。方法。通过 RT-PCR 和免疫组织化学检查正常子宫内膜腺体和癌细胞系中 DCC 和 netrin-1 的表达。观察外源DCC和netrin-1表达的影响以及各自表达载体的转染。结果。增殖期和分泌早期的子宫内膜腺体同时表达 DCC 和 netrin-1，但分泌晚期的子宫内膜腺体倾向于沉默 DCC 表达。此外，所有子宫内膜癌细胞系都失去了正常的 DCC 表达。在缺乏 netrin-1 诱导的细胞凋亡的情况下恢复癌细胞系中的 DCC 表达。然而，在 netrin-1 存在的情况下没有观察到任何变化。结论。我们的观察表明，DCC/netrin-1 信号传导可能使细胞经历子宫内膜腺体结构或功能从增殖期向分泌期的转变。此外，DCC表达的沉默可能有助于子宫内膜癌细胞逃离DCC调节的凋亡程序，从而促进恶性表型。 (C) 2004 Elsevier Inc. 保留所有权利。
Objective. Although DCC has been considered as a candidate tumor suppressor, the roles it plays in the uterine endometrium and in the carcinogenic process remains unclear. To define these roles more clearly, we examined the expression of DCC and its ligand, netrin-1, in the normal endometrium and in endometrial cancer.Methods. The expression of DCC and netrin-1 in normal endometrial glands and in cancer cell lines was examined by RT-PCR and immunohistochemistry. The effects of exogenous DCC and netrin-1 expression were observed together with the respective expression vector transfection.Results. Endometrial glands in the proliferative and early secretory phase expressed both DCC and netrin-1, but glands in the latesecretory phase tended to silence DCC expression. In addition, all of the endometrial cancer cell lines lost normal DCC expression. Restored DCC expression in the cancer cell lines in the absence of netrin-1 induced apoptosis. However, no changes were observed in the presence of netrin-1.Conclusion. Our observations suggest that DCC/netrin-1 signaling may commit cells to the transition of endometrial gland architecture or function from a proliferating to a secretory phase. In addition, the silencing of DCC expression may contribute to the escape of endometrial cancer cells from a DCC-regulated apoptotic program, thereby promoting malignant phenotypes. (C) 2004 Elsevier Inc. All rights reserved.