Veldscholte J, Ris-Stalpers C, Kuiper G G, Jenster G, Berrevoets C, Claassen E, van Rooij H C, Trapman J, Brinkmann A O, Mulder E
Department of Biochemistry II, Erasmus University Rotterdam, The Netherlands.
Biochem Biophys Res Commun. 1990 Dec 14;173(2):534-40. doi: 10.1016/s0006-291x(05)80067-1.
LNCaP prostate tumor cells contain an abnormal androgen receptor 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 LNCaP 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.
LNCaP前列腺肿瘤细胞含有异常的雄激素受体系统。孕激素、雌二醇和抗雄激素能与雄激素竞争结合雄激素受体，并能刺激细胞生长和前列腺特异性酸性磷酸酶的分泌。我们在LNCaP雄激素受体的配体结合域中发现了一个单点突变，该突变改变了密码子868（苏氨酸突变为丙氨酸）的编码意义。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、雌激素和抗雄激素能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，该突变影响了不同类固醇和抗类固醇对基因表达的结合和诱导作用。
