A MUTATION IN THE LIGAND-BINDING DOMAIN OF THE ANDROGEN RECEPTOR OF HUMAN LNCAP CELLS AFFECTS STEROID BINDING CHARACTERISTICS AND RESPONSE TO ANTI-ANDROGENS
A MUTATION IN THE LIGAND-BINDING DOMAIN OF THE ANDROGEN RECEPTOR OF HUMAN LNCAP CELLS AFFECTS STEROID BINDING CHARACTERISTICS AND RESPONSE TO ANTI-ANDROGENS
复制标题
DOI：
10.1016/s0006-291x(05)80067-1
复制
发表时间：
1990-12-14
影响因子：
3.1
通讯作者：
MULDER, E
中科院分区：
文献类型：
--
作者：
VELDSCHOLTE, J;RISSTALPERS, C;MULDER, E
LNCAP前列腺肿瘤细胞含有异常的雄激素受体系统。孕激素、雌二醇和抗雄激素可与雄激素竞争结合雄激素受体，并可刺激细胞生长和前列腺特异性酸性磷酸酶分泌。我们已经发现在INCaP雄激素受体的单点突变改变的配体结合结构域中的密码子868（苏氨酸丙氨酸）的意义。将含有正常或突变雄激素受体序列的表达载体转染到COS或HeLa细胞中。雄激素、孕激素、雌激素和抗雄激素结合突变的雄激素受体蛋白并激活雄激素调节的报告基因构建体（GRE-tk-cat）的表达。因此，突变影响不同类固醇和抗类固醇的结合和基因表达的诱导。
LNCAP prostate tumor cells contain an abnormal androgen receptors system. Progestagens, estradiol and anti-androgens can compete with androgens for binding to the androgen receptor and can stimulate both cell growth and excretion of prostate specific acid phosphatase. We have discovered in the INCaP androgen receptor a single point mutation changing the sense of codon 868 (Thr to Ala) in the ligand binding domain. Expression vectors containing the normal or mutated androgen receptor sequence were transfected into COS or HeLa cells. Androgens, progestagens, estrogens and anti-androgens bind the mutated androgen receptor protein and activate the expression of an androgen-regulated reporter gene construct (GRE-tk-cat). The mutation therefore influences both binding and the induction of gene expression by different steroids and antisteroids.