子宫 UDP-葡糖醛酸基转移酶 1A8（UGT1A8）和 UDP-葡糖醛酸基转移酶 2B7（UGT2B7）的功能涉及到基于雌激素代谢调节的子宫内膜癌。

The function of uterine UDP-glucuronosyltransferase 1A8 (UGT1A8) and UDP-glucuronosyltransferase 2B7 (UGT2B7) is involved in endometrial cancer based on estrogen metabolism regulation.

机构信息

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, China.

Department of Pharmacy, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

出版信息

Hormones (Athens). 2020 Sep;19(3):403-412. doi: 10.1007/s42000-020-00213-x. Epub 2020 Jun 26.

DOI:10.1007/s42000-020-00213-x

PMID:32592099

Abstract

BACKGROUND

The progression of endometrial cancer (EC) is closely related to estrogen levels. UDP-glucuronosyltransferases (UGTs) are an essential class of phase II metabolizing enzymes that play a pivotal role in detoxifying steroid hormone.

PURPOSE

In this study, we aimed to uncover the role of UGTs in estrogen metabolism and the pathogenesis of EC.

METHODS

A total of 100 unrelated EC patients (mean age 52.15 ± 10.04 y) and 100 healthy subjects (mean age 50.26 ± 8.80 y) were recruited for analysis of the UGT gene polymorphism and estrogen level. In six cases of EC, EC-adjacent tissues and cancer tissues were collected for detection of UGT expression.

RESULTS

Our results showed that the estrogen homeostasis profile was disturbed in EC patients, with carcinogenic catechol estrogens (4-OHE1, 2-OHE1, 2-OHE2) significantly accumulated in the serum of these patients. Also, levels of estrogen-glucuronides were decreased significantly, and the expression of UGT1A8 and UGT2B7 in uterine tissues was downregulated in EC patients. Consistent with this, we observed that the distribution of genotypes and allele frequencies in UGT1A8 rs1042597 and UGT2B7 rs7439366 was significantly different between EC patients and healthy volunteers.

CONCLUSION

These results indicated that UGT1A8 and UGT2B7 may contribute to the estrogen signaling pathway and the pathogenesis of EC.

摘要

背景

子宫内膜癌（EC）的进展与雌激素水平密切相关。UDP-葡萄糖醛酸基转移酶（UGTs）是一种重要的 II 相代谢酶，在类固醇激素解毒中起关键作用。

目的

本研究旨在揭示 UGT 在雌激素代谢和 EC 发病机制中的作用。

方法

共纳入 100 例无关的 EC 患者（平均年龄 52.15±10.04 岁）和 100 例健康对照者（平均年龄 50.26±8.80 岁），分析 UGT 基因多态性和雌激素水平。在 6 例 EC 患者中，收集 EC 相邻组织和癌组织检测 UGT 表达。

结果

结果显示，EC 患者的雌激素内稳态紊乱，致癌儿茶酚雌激素（4-OHE1、2-OHE1、2-OHE2）在这些患者的血清中明显积累。此外，雌激素葡萄糖醛酸苷水平显著降低，UGT1A8 和 UGT2B7 在子宫组织中的表达下调。与这一结果一致，我们观察到 UGT1A8 rs1042597 和 UGT2B7 rs7439366 的基因型和等位基因频率在 EC 患者和健康志愿者之间的分布存在显著差异。