Regulation of Estradiol Synthesis by Aromatase Interacting Partner in Breast (AIPB).
Regulation of Estradiol Synthesis by Aromatase Interacting Partner in Breast (AIPB).
复制标题
乳房中芳香酶相互作用伙伴 (AIPB) 对雌二醇合成的调节。
DOI：
10.1128/mcb.00357-21
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发表时间：
2021
影响因子：
5.3
通讯作者：
Burak,WilliamE
中科院分区：
文献类型：
--
作者：
Bose,HimangshuS;Whittal,RandyM;Lanier,CurtisE;Marshall,Brendan;Rajapaksha,Maheshinie;Wheeler,BrianW;Carbo,NicholasD;Hahn,ElinM;Perry,ElizabethW;Hall,NealM;Melomed,MikhailM;Perkins,EdwardL;Burak,WilliamE
雌二醇对于女性性征和生育能力的发展是必不可少的。绝经后妇女和乳腺癌患者的雌二醇水平很高。芳香酶催化雌二醇的合成；然而，调节芳香酶活性的因素尚不清楚。我们从人乳腺组织的内质网中鉴定出一种新的22 kDa蛋白质--乳房芳香酶相互作用伙伴(AIPB)。AIPB在致癌乳腺中的表达降低，在三阴性肿瘤中进一步降低。与芳香酶一样，AIPB的表达也是由非甾体雌激素诱导的。我们发现AIPB和芳香酶在非致瘤和致瘤的乳腺组织和细胞中相互作用。在肿瘤细胞中，有条件的AIPB过表达降低了雌二醇，而用AIPB结合抗体阻断AIPB的可用性则增加了雌二醇。在AIPB基因敲除的细胞中，雌二醇的合成高度增加，这表明新发现的AIPB蛋白对芳香酶活性是重要的，并且是雌二醇合成的关键调节器。因此，AIPB蛋白表达的改变可能代表肿瘤发生的早期事件，并预测发生乳腺癌的风险增加。
Estradiol is essential for the development of female sex characteristics and fertility. Postmenopausal women and breast cancer patients have high levels of estradiol. Aromatase catalyzes estradiol synthesis; however, the factors regulating aromatase activity are unknown. We identified a new 22-kDa protein, aromatase interacting partner in breast (AIPB), from the endoplasmic reticulum of human breast tissue. AIPB expression is reduced in tumorigenic breast and further reduced in triple-negative tumors. Like that of aromatase, AIPB expression is induced by nonsteroidal estrogen. We found that AIPB and aromatase interact in nontumorigenic and tumorigenic breast tissues and cells. In tumorigenic cells, conditional AIPB overexpression decreased estradiol, and blocking AIPB availability with an AIPB-binding antibody increased estradiol. Estradiol synthesis is highly increased in AIPB knockdown cells, suggesting that the newly identified AIPB protein is important for aromatase activity and a key modulator of estradiol synthesis. Thus, a change in AIPB protein expression may represent an early event in tumorigenesis and be predictive of an increased risk of developing breast cancer.