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雌激素对正常和恶性子宫内膜组织中基因表达的调控

Oestrogen regulated gene expression in normal and malignant endometrial tissue.

作者信息

O'Toole Sharon A, Dunn Elizabeth, Sheppard Brian L, Sheils Orla, O'Leary John J, Wuttke Wolfgang, Seidlova-Wuttke Dana

机构信息

Obstetrics and Gynaecology, Trinity College Dublin, Trinity Centre, St. James's Hospital, Dublin 8, Ireland.

出版信息

Maturitas. 2005 Jun 16;51(2):187-98. doi: 10.1016/j.maturitas.2004.07.009.

Abstract

OBJECTIVES

The aim of this study was to examine the expression of oestrogen regulated genes in premenopausal and postmenopausal normal and malignant endometrial specimens. The molecular mechanisms and the role of these genes in endometrial carcinogenesis are poorly understood.

METHODS

Normal and malignant endometrial specimens were collected from patients undergoing hysterectomy. Real time TaqMan PCR was used to examine the mRNA expression levels of oestrogen receptor a (ERa) and b (ERb), progesterone receptor (PR), insulin like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF).

RESULTS

Expression analysis was carried out on 60 patients. ERa was more predominantly expressed in the endometrial samples than ERb, 28% of the specimens did not express ER. Normal pre and postmenopausal tissue expressed higher levels of ERa, PR and IGF-1 than malignant tissue. ERa and PR expression was significantly higher in the proliferative phase endometrium compared to the secretory phase (P < 0.05). PR mRNA expression was significantly correlated with ERa in all tissue types.

CONCLUSIONS

ERa expression may play an important role in the regulation of PR in normal and malignant endometrium. Further work is needed to establish if IGF-1 plays a role in a subset of endometrial cancers and if isoforms of VEGF play a role in endometrial cancer.

摘要

目的

本研究旨在检测雌激素调节基因在绝经前和绝经后正常及恶性子宫内膜标本中的表达情况。目前对这些基因在子宫内膜癌发生过程中的分子机制及作用了解甚少。

方法

从接受子宫切除术的患者中收集正常和恶性子宫内膜标本。采用实时TaqMan PCR检测雌激素受体α(ERα)、雌激素受体β(ERβ)、孕激素受体(PR)、胰岛素样生长因子1(IGF-1)和血管内皮生长因子(VEGF)的mRNA表达水平。

结果

对60例患者进行了表达分析。ERα在子宫内膜样本中的表达比ERβ更占优势,28%的标本不表达ER。绝经前和绝经后的正常组织中ERα、PR和IGF-1的表达水平高于恶性组织。与分泌期相比,增殖期子宫内膜中ERα和PR的表达显著更高(P < 0.05)。在所有组织类型中,PR mRNA表达与ERα显著相关。

结论

ERα表达可能在正常和恶性子宫内膜中PR的调节中起重要作用。需要进一步研究以确定IGF-1是否在一部分子宫内膜癌中起作用,以及VEGF的亚型是否在子宫内膜癌中起作用。

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