Augmented cell survival in eutopic endometrium from women with endometriosis: Expression of c-myc, TGF-betaI and bax genes
Augmented cell survival in eutopic endometrium from women with endometriosis: Expression of c-myc, TGF-betaI and bax genes
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DOI：
10.1186/1477-7827-3-45
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发表时间：
2005-09-08
影响因子：
4.4
通讯作者：
Boric, MA
中科院分区：
文献类型：
--
作者：
Johnson, MC;Torres, M;Boric, MA
背景：子宫内膜异位症是一种常见的妇科疾病，其特征是子宫内膜组织存在于子宫外。正常月经中的碎片由坏死细胞和活细胞组成，由于程序性细胞死亡，它们在异位位置无法存活。本研究的目的是通过研究 bax（促凋亡）、c-myc（细胞周期调节因子）和 TGF-β1（参与细胞分化）基因，评估子宫内膜异位症女性在位子宫内膜在整个月经周期中细胞增殖和凋亡之间的平衡是否发生变化。方法：在位子宫内膜取自：30 名子宫内膜异位症女性（32.8 +/- 5 岁）和 34 名生育女性月经正常的女性（36 +/- 5.3 岁）。我们分析了细胞凋亡（TUNEL：DNA 片段化）；细胞增殖（Ki67 的免疫组织化学 (IHC)）；子宫内膜外植体中的 c-myc、bax 和 TGF-β1 mRNA 丰度 (RT-PCR) 和 TGF-β1 蛋白 (IHC)。结果：在两种子宫内膜中，腺体中的细胞增殖从增殖期到分泌后期强烈减少，但间质中的细胞增殖却没有明显减少。患有子宫内膜异位症的增殖性子宫内膜的腺体和间质的阳性染色分别比对照子宫内膜高 1.9 倍和 2.2 倍 (p < 0.05)。子宫内膜异位症增生性子宫内膜中 c-myc mRNA 的丰度比正常组织高 65% (p < 0.05)。正常子宫内膜中 TGF-β1（mRNA 和蛋白）在分泌中期增强，但在子宫内膜异位症子宫内膜中未观察到这种效应。在正常子宫内膜中，在分泌后期，凋亡的上皮细胞和基质细胞的百分比增加了30倍以上。相比之下，在子宫内膜异位症的子宫内膜中，不仅没有观察到这种增加，而且与正常子宫内膜相比，bax mRNA 减少了 63% (p < 0.05)。在早期分泌期，凋亡的基质细胞增加了 10 倍，同时子宫内膜异位症的子宫内膜中 bax mRNA 丰度增加 (42%) (p < 0.05)。结论：在子宫内膜异位症的在位子宫内膜中观察到 c-myc、TGF-β1 和 bax 的表达发生改变，表明其参与了该疾病中细胞存活的调节。由于细胞凋亡导致的细胞死亡减少，并且细胞增殖增加，这些患者的在位子宫内膜中细胞活力增强，表明这种情况可能促进子宫内膜的侵袭特征。
Background: Endometriosis is a common gynaecological disorder characterized by the presence of endometrial tissue outside of the uterus. The fragments in normal menstruation are composed of necrotic and living cells, which do not survive in ectopic locations because of programmed cell death. The aim of this study was to evaluate if the balance between cell proliferation and apoptosis is changed in eutopic endometrium from women with endometriosis throughout the menstrual cycle by studying bax ( proapoptotic), c-myc ( regulator of cell cycle) and TGF-beta1 ( involved in cell differentiation) genes.Methods: Eutopic endometrium was obtained from: 30 women with endometriosis (32.8 +/- 5 years) and 34 fertile eumenorrheic women ( 36 +/- 5.3 years). We analyzed apoptosis ( TUNEL: DNA fragmentation); cell proliferation ( immunohistochemistry (IHC) for Ki67); c-myc, bax and TGF-beta1 mRNA abundance (RT-PCR) and TGF-beta1 protein ( IHC) in endometrial explants.Results: Cell proliferation strongly decreased from proliferative to late secretory phases in glands, but not in stroma, in both endometria. Positive staining in glands and stroma from proliferative endometrium with endometriosis was 1.9- and 2.2-fold higher than control endometrium, respectively ( p < 0.05). Abundance of c-myc mRNA was 65% higher in proliferative endometrium from endometriosis than normal tissue ( p < 0.05). TGF-beta1 ( mRNA and protein) augmented during mid secretory phase in normal endometrium, effect not observed in endometrium with endometriosis. In normal endometrium, the percentage of apoptotic epithelial and stromal cells increased more than 30-fold during late secretory phase. In contrast, in endometrium from endometriosis, not only this increase was not observed, besides bax mRNA decreased 63% versus normal endometrium ( p < 0.05). At once, in early secretory phase, apoptotic stromal cells increased 10-fold with a concomitant augment of bax mRNA abundance (42%) in endometria from endometriosis ( p < 0.05).Conclusion: An altered expression of c-myc, TGF-beta1 and bax was observed in eutopic endometrium from endometriosis, suggesting its participation in the regulation of cell survival in this disease. The augmented cell viability in eutopic endometrium from these patients as a consequence of a reduction in cell death by apoptosis, and also an increase in cell proliferation indicates that this condition may facilitate the invasive feature of the endometrium.