Milczarek Ryszard, Klimek Jerzy
Department of Pharmaceutical Biochemistry, Medical University of Gdańsk, 1 Debinki St., 80-211 Gdańsk, Poland.
Postepy Biochem. 2005;51(4):430-9.
Estrogens control a large range pivotal life functions as reproductive development and fertility, bone growth and sexual behavior. Aromatase is a key enzyme of estrogen biosynthesis. The property, structure and reaction mechanism of aromatase as well as detailed structure of human aromatase cytochrome P450 gene (CYP19) was discussed in this article. It was pointed that unique human CYP19 gene expression results from presence of many tissue specific promoters and alternative splicing. The molecular mechanism of control aromatase cytochrome P450 gene expression in various species ovaries, testes and human adipose tissue and placenta was discussed in details. Because of a very important role of estrogen in breast cancer a molecular base of aberrant expression CYP19 gene in breast tumor and adipose tissue proximal to breast tumor and potential possibility of pharmacological silencing of this gene expression was discussed in the article.
雌激素控制着一系列关键的生命功能,如生殖发育、生育能力、骨骼生长和性行为。芳香化酶是雌激素生物合成的关键酶。本文讨论了芳香化酶的性质、结构和反应机制以及人芳香化酶细胞色素P450基因(CYP19)的详细结构。指出独特的人CYP19基因表达源于许多组织特异性启动子的存在和可变剪接。详细讨论了在各种物种的卵巢、睾丸以及人脂肪组织和胎盘中控制芳香化酶细胞色素P450基因表达的分子机制。由于雌激素在乳腺癌中起着非常重要的作用,本文还讨论了乳腺肿瘤及乳腺肿瘤附近脂肪组织中CYP19基因异常表达的分子基础以及该基因表达的药理学沉默的潜在可能性。