Current knowledge of the multifunctional 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1).
Current knowledge of the multifunctional 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1).
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DOI：
10.1016/j.gene.2016.04.031
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发表时间：
2016-08-15
期刊：
影响因子：
3.5
通讯作者：
Lin SX
中科院分区：
文献类型：
--
作者：
He W;Gauri M;Li T;Wang R;Lin SX
20世纪40年代末，17β-HSD1作为17β-HSD家族的第一个成员被发现，其基因被克隆。人类17β-HSD1的三维结构是人类类固醇转化酶的第一个例子。因此，近二十年来，人类酶的结构和生物学功能得到了广泛的研究。在人类中，这种酶在胎盘、卵巢、子宫内膜和乳房中表达。雌激素激活的高活性为17β-HSD1在乳腺癌、子宫内膜异位症和非小细胞肺癌等雌激素依赖性疾病中的作用提供了依据。其雌激素激活和雄激素失活的双重功能已在分子水平和乳腺癌细胞水平上被揭示，显著刺激乳腺癌细胞的增殖。临床样本证实了该酶在乳腺癌中的过表达。抑制人17β-HSD1导致异种移植肿瘤缩小。不幸的是，经过几十年的研究，仍然没有使用这种酶抑制剂的药物。这是由于难以摆脱其抑制剂的雌激素活性，这些抑制剂大多是雌激素类似物。新的非甾体抑制剂为该酶的非雌激素抑制剂提供了新的希望。
At the late 1940s, 17β-HSD1 was discovered as the first member of the 17β-HSD family with its gene cloned. The three-dimensional structure of human 17β-HSD1 is the first example of any human steroid converting enzyme. The human enzyme's structure and biological function have thus been studied extensively in the last two decades. In humans, the enzyme is expressed in placenta, ovary, endometrium and breast. The high activity of estrogen activation provides the basis of 17β-HSD1's implication in estrogen-dependent diseases, such as breast cancer, endometriosis and non-small cell lung carcinomas. Its dual function in estrogen activation and androgen inactivation has been revealed in molecular and breast cancer cell levels, significantly stimulating the proliferation of such cells. The enzyme's overexpression in breast cancer was demonstrated by clinical samples. Inhibition of human 17β-HSD1 led to xenograft tumor shrinkage. Unfortunately, through decades of studies, there is still no drug using the enzyme's inhibitors available. This is due to the difficulty to get rid of the estrogenic activity of its inhibitors, which are mostly estrogen analogues. New non-steroid inhibitors for the enzyme provide new hope for non-estrogenic inhibitors of the enzyme.
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影响因子：
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