最近有关酶参与雌激素形成的控制和转换在人类乳腺癌。

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Pasqualini JR Chetrite GS

最近有关酶参与雌激素形成的控制和转换在人类乳腺癌。

93年2月J类固醇生物化学杂志。2005;(2 - 5):221 - 36。

PubMed ID

15860265 (在PubMed

]

文摘

绝大多数乳腺癌的早期激素依赖性和广泛接受,雌二醇(E2)中扮演一个重要的角色在这个肿瘤的起源和演化。人类乳腺癌组织中包含所有的酶:雌激素酮硫酸酯酶,17 beta-hydroxysteroid脱氢酶,芳香化酶参与E2 bioformation的最后步骤。Sulfotransferases雌激素转化为生物活性雌激素的硫酸盐也存在于这个组织。定量数据表明,硫酸酯酶通路,将雌激素硫酸盐转化为生物活性非结合的E2,是100 - 500倍的“芳香化酶通路”,将雄激素转化为雌激素。治疗乳腺癌患者anti-aromatases主要发展有非常积极的结果。然而,通过硫酸酯酶通路的E2的形成是非常重要的在乳腺癌组织中。近年来人们发现抗雌激素(如三苯氧胺、4-hydroxytamoxifen),各种黄体酮(例如promegestone、醋酸nomegestrol medrogestone, dydrogesterone, norelgestromin), tibolone及其代谢物,以及其他甾类(如氨基磺酸盐)和非甾体类化合物,是强有力的硫酸酯酶抑制剂。在另一个系列的研究,发现E2本身有很强的anti-sulfatase行动。这个矛盾的影响,这种激素E2添加一个新的生物反应和可能与雌激素替代疗法,观察有任何影响或减少绝经后妇女的乳腺癌死亡率。有趣的信息是类固醇硫酸酯酶的高表达mRNA预测患者预后不良+ ER。 These progestins, as well as tibolone, can also block the conversion of estrone to estradiol by the inhibition of the 17beta-hydroxysteroid dehydrogenase type I (17beta-HSD-1). High expressison of 17beta-HSD-1 can be an indicator of adverse prognosis in ER-positive patients. It was shown that nomegestrol acetate, medrogestone, promegestone or tibolone, could stimulate the sulfotransferase activity for the local production of estrogen sulfates. This is an important point in the physiopathology of this disease, as it is well known that estrogen sulfates are biologically inactive. A possible correlation between this stimulatory effect on sulfotransferase activity and breast cancer cell proliferation is presented. In agreement with all this information, we have proposed the concept of selective estrogen enzyme modulators (SEEM). In conclusion, the blockage in the formation of estradiol via sulfatase, or the stimulatory effect on sulfotransferase activity in combination with anti-aromatases can open interesting and new possibilities in clinical applications in breast cancer.

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药物酶

药物	酶	类	生物	药理作用	行动
Norelgestromin	Steryl-sulfatase	蛋白质	人类	未知的	抑制剂	细节