Estrogen-metabolizing enzymes in breast cancers from women over the age of 80 years
Estrogen-metabolizing enzymes in breast cancers from women over the age of 80 years
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DOI：
10.1210/jc.2005-1967
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发表时间：
2006-02-01
影响因子：
5.8
通讯作者：
Harada, N
中科院分区：
文献类型：
--
作者：
Honma, N;Takubo, K;Harada, N
背景：芳香化酶、类固醇硫酸酯酶和17 β -羟基类固醇脱氢酶1型（HSD-1）外周上调，而雌激素硫转移酶（EST）和HSD-2下调，合成活性更强的雌激素。这些雌激素代谢酶（EMEs）在绝经后乳腺癌中很重要，但从未在老年人乳腺癌中进行过系统的研究。目的和设计：比较39例老年患者（年龄80-99岁）癌性和正常乳腺组织中EMEs的mRNA水平（对照37-70岁），或根据雌激素(ER)/孕酮（PR）受体状态进行比较。结果：老年人癌症（EldCa）中芳香化酶水平高于老年人正常组织（P = 0.0008）或对照组（P = 0.0033）。相比之下，肿瘤组织中类固醇硫酸酯酶和EST的水平高于正常组织（P = 0.0046和P < 0.0001）或EldCa （P < 0.0001和P < 0.0001）。HSD-1和HSD-2的水平在任何两个类别之间都没有显著差异。在EldCa中，ER/ pr阳性的HSD-1水平高于ER/ pr阴性的癌，而EST和HSD-2的结果相反。结论：芳香化酶在EldCa中的重要性相对增加。与ER/ pr阴性的EldCa相比，ER/ pr阳性的EldCa表现出更有利于雌激素产生的EMEs模式。在EldCa中显示的特殊模式可能阐明了EMEs在卵巢癌发病机制中卵巢雌激素缺乏的作用。
Context: Aromatase, steroid sulfatase, and 17 beta-hydroxysteroid dehydrogenase type 1 (HSD-1) peripherally up-regulate, whereas estrogen sulfotransferase ( EST) and HSD-2 down-regulate, the synthesis of active and more potent estrogens. These estrogen-metabolizing enzymes (EMEs) are important in postmenopausal breast cancers, but have never been systematically examined in breast cancers of the elderly.Objective and Design: mRNA levels of EMEs in cancerous and normal breast tissues from 39 elderly patients (age, 80-99 yr) were compared with those from 39 controls (age, 37-70 yr) or compared according to estrogen (ER)/progesterone (PR) receptor status.Results: Aromatase levels were higher in cancers of the elderly (EldCa) than in normal tissue of the elderly (P = 0.0008) or cancers of controls (P = 0.0033). In contrast, levels of steroid sulfatase and EST were higher in cancers of controls than normal tissue of controls (P = 0.0046 and P < 0.0001, respectively) or EldCa (P < 0.0001 and P < 0.0001, respectively). Levels of HSD-1 and HSD-2 did not differ significantly between any two of the categories. Among EldCa, HSD-1 levels were higher in ER/PR-positive than in ER/PR-negative carcinomas, whereas EST and HSD-2 exhibited opposite results.Conclusions: The importance of aromatase is relatively increased in EldCa. ER/ PR-positive EldCa exhibited a pattern of EMEs more beneficial to the production of estrogen than did ER/PR-negative EldCa. The specific pattern exhibited in EldCa may elucidate the role of EMEs in the absence of ovarian estrogens in the pathogenesis of breast cancer.