Microsomal epoxide hydrolase expression in the endometrial uterine corpus is regulated by progesterone during the menstrual cycle

Microsomal epoxide hydrolase expression in the endometrial uterine corpus is regulated by progesterone during the menstrual cycle
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DOI:
10.1007/s10735-010-9266-6
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发表时间:
2010-04-01
影响因子:
3.2
通讯作者:
Knabbe, Cornelius
Knabbe, Cornelius
中科院分区:
生物学4区
文献类型:
--
作者:
Popp, Simone L.;Abele, Ina S.;Knabbe, Cornelius

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我们之前的研究表明,微粒体环氧化物水解酶(mEH)的高表达水平与接受他莫昔芬治疗的乳腺癌患者预后不良相关,这表明mEH表达的增强可能导致抗雌激素抵抗(Fritz等人,journal clinical oncology, 19:3- 9,2001)。因此,本研究的目的是深入了解mEH在激素反应组织中的作用。我们通过免疫组化染色分析子宫内膜活检样本,指出mEH在月经周期中的调节:在前半期mEH表达低,在后半期增加,在怀孕期间达到最高水平。此外,我们选择孕激素受体(PR)阳性的人子宫内膜细胞系IKPRAB-36(雌激素受体α [ER α]阴性)和ECC1-PRAB72 (ER α阳性)进一步研究激素对mEH表达的调节。Western Blot和定量RT-PCR分析显示,含ER α的ECC1-PRAB72细胞经羟孕酮17-醋酸酯(MPA)处理后mEH表达增加。相反,我们的结果表明,MPA对ER α - IKPRAB-36细胞的mEH蛋白水平没有影响。综上所述,在pr和ER α存在的情况下,mEH的表达受黄体酮的调控。
We have shown previously that high expression levels of microsomal epoxide hydrolase (mEH) correlate with a poor prognosis of breast cancer patients receiving tamoxifen, suggesting that enhanced mEH expression could lead to antiestrogen resistance (Fritz et al. in J Clin Oncol 19:3-9, 2001). Thus, the purpose of this study was to gain insights into the role of mEH in hormone-responsive tissues. We analyzed biopsy samples of the endometrium by immunohistochemical staining, pointing to a regulation of mEH during the menstrual cycle: during the first half mEH expression was low, increased during the second half and reached highest levels during pregnancy. Additionally, the progesterone receptor (PR) positive human endometrial cell lines IKPRAB-36 (estrogene receptor alpha [ER alpha] negative) and ECC1-PRAB72 (ER alpha positive) were chosen to further investigate the hormonal regulation of mEH expression. Western Blot and quantitative RT-PCR analysis revealed an increase of mEH expression after treatment with medroxy-progesterone 17-acetate (MPA) in the ER alpha containing ECC1-PRAB72 cells. In contrast our results suggest that MPA had no influence on the mEH protein level in the ER alpha- IKPRAB-36 cells. In conclusion, mEH expression is regulated by progesterone in the presence of both PRs and ER alpha.