Expression of nodal signalling components in cycling human endometrium and in endometrial cancer
Expression of nodal signalling components in cycling human endometrium and in endometrial cancer
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DOI：
10.1186/1477-7827-7-122
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发表时间：
2009-10-29
影响因子：
4.4
通讯作者：
Harrison, Craig A.
中科院分区：
文献类型：
--
作者：
Papageorgiou, Irene;Nicholls, Peter K.;Harrison, Craig A.
背景：人类子宫内膜在其整个成年生殖生活中不断重塑的能力是独一无二的。虽然子宫内膜的组织损伤和破裂过程已经得到了很好的研究，但对月经后子宫内膜如何再生却知之甚少。Nodal是转化生长因子-β超家族的成员，调节早期胚胎发育过程中模式形成和分化的过程。（共受体）和Lefty A通过RT-PCR和免疫组织化学方法在月经周期和子宫内膜癌中检测（拮抗剂）。Nodal和Cripto被发现在月经周期的增殖期在基质细胞和上皮细胞中以高水平表达。虽然在表面和腺上皮的蛋白质的免疫反应性保持在相对稳定的状态水平，在整个周期，其表达显着下降的中间分泌期的间质隔室。如先前所报道的，Lefty表达主要限于分泌后期和月经期的腺上皮和周围基质。最近的研究表明，Nodal途径活性在许多人类癌症中上调，我们发现，Nodal和Cripto免疫反应性在从组织学1级到组织学2级和3级子宫内膜癌的过渡中显著增加。引人注目的是，Lefty的表达是低的或不存在的所有癌tissue.Conclusion：Nodal在正常和恶性子宫内膜细胞，缺乏Lefty的表达强烈支持的重要作用，这种胚胎形态发生在整个月经周期和肿瘤发生的组织重塑事件。
Background: The human endometrium is unique in its capacity to remodel constantly throughout adult reproductive life. Although the processes of tissue damage and breakdown in the endometrium have been well studied, little is known of how endometrial regeneration is achieved after menstruation. Nodal, a member of the transforming growth factor-beta superfamily, regulates the processes of pattern formation and differentiation that occur during early embryo development.Methods: In this study, the expression of Nodal, Cripto (co-receptor) and Lefty A (antagonist) was examined by RT-PCR and immunohistochemistry across the menstrual cycle and in endometrial carcinomas.Results: Nodal and Cripto were found to be expressed at high levels in both stromal and epithelial cells during the proliferative phase of the menstrual cycle. Although immunoreactivity for both proteins in surface and glandular epithelium was maintained at relatively steady-state levels across the cycle, their expression was significantly decreased within the stromal compartment by the mid-secretory phase. Lefty expression, as has previously been reported, was primarily restricted to glandular epithelium and surrounding stroma during the late secretory and menstrual phases. In line with recent studies that have shown that Nodal pathway activity is upregulated in many human cancers, we found that Nodal and Cripto immunoreactivity increased dramatically in the transition from histologic Grade 1 to histologic Grades 2 and 3 endometrial carcinomas. Strikingly, Lefty expression was low or absent in all cancer tissues.Conclusion: The expression of Nodal in normal and malignant endometrial cells that lack Lefty strongly supports an important role for this embryonic morphogen in the tissue remodelling events that occur across the menstrual cycle and in tumourogenesis.