Smuc Tina, Rizner Tea Lanisnik
Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
Mol Cell Endocrinol. 2009 Mar 25;301(1-2):74-82. doi: 10.1016/j.mce.2008.09.019. Epub 2008 Sep 27.
Endometrial cancer is related to estrogen stimulation not opposed by progesterone. We have examined expression of the pre-receptor regulatory enzymes aromatase, 17beta-hydroxysteroid dehydrogenases (17beta-HSDs), 20alpha-hydroxysteroid dehydrogenases (20alpha-HSDs), sulfatase and sulfotransferase, and estrogen (ERs) and progesterone (PRs) receptors in samples of endometrial cancer and adjacent normal endometrium. No significant gene up-regulation was seen, although aromatase, AKR1C3, a 17beta-HSD and 20alpha-HSD, and AKR1C1, the major 20alpha-HSD, were up-regulated in 50% of samples. Significant down-regulation was seen for 17beta-HSD types 1 and 7, sulfotransferase, ERalpha, ERbeta, PR-AB. Western blotting revealed higher levels of AKR1C3 and PR-B and lower levels of ERalpha in cancerous endometrium, and immunohistochemistry confirmed expression of AKR1C3, PR-B and ERalpha at the cellular level. Up-regulation of aromatase in concert with AKR1C3 can lead to increased levels of estradiol, which acts via ERalpha. Up-regulation of AKR1C1 and AKR1C3 can result in lower levels of the protective progesterone, which acts mainly via PR-B.
子宫内膜癌与未受孕酮拮抗的雌激素刺激有关。我们检测了子宫内膜癌样本及相邻正常子宫内膜中受体前调节酶芳香化酶、17β-羟基类固醇脱氢酶（17β-HSDs）、20α-羟基类固醇脱氢酶（20α-HSDs）、硫酸酯酶和磺基转移酶，以及雌激素（ERs）和孕激素（PRs）受体的表达。尽管芳香化酶、AKR1C3（一种17β-HSD和20α-HSD）以及主要的20α-HSD即AKR1C1在50%的样本中上调，但未观察到显著的基因上调。1型和7型17β-HSD、磺基转移酶、ERα、ERβ、PR-AB出现显著下调。蛋白质印迹法显示癌性子宫内膜中AKR1C3和PR-B水平较高，ERα水平较低，免疫组织化学在细胞水平证实了AKR1C3、PR-B和ERα的表达。芳香化酶与AKR1C3协同上调可导致雌二醇水平升高，其通过ERα发挥作用。AKR1C1和AKR1C3上调可导致主要通过PR-B发挥作用的保护性孕激素水平降低。
