PSA基因启动子中一个与雄激素调节相关的序列  被引量:3

A Sequence in the PSA Gene Promoter Which Involved in Androgen Regulation of the Gene

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作  者:张建业[1] 庞维秋[1] 王鑫[1] 张莲英[1] 茹炳根[2] 

机构地区:[1]山东医科大学生物化学教研室,济南250012 [2]北京大学生命科学学院,北京100871

出  处:《生物化学与生物物理进展》1997年第3期228-232,共5页Progress In Biochemistry and Biophysics

摘  要:人前列腺特异抗原 (PSA)基因的表达受雄激素的调节 ,其雄激素应答元件 (ARE)位于-1 70附近 .为了确定雄激素对该基因的诱导作用是否受ARE上游序列的影响 ,把PSA启动子区的不同长度的天然的和变异的DNA片段分别与报告基因CAT相连 ,构建了不同的 pBLCAT3 PSA质粒 .用它们转染人前列腺肿瘤细胞PC 3.结果表明 1 5bp的RF1 5序列 ( -34 0~ -32 6)的缺失和变异可显著降低雄激素的诱导作用 .区带转移测定表明人前列腺肿瘤细胞LNcap和PC 3中的某些核内调节蛋白可与RF1 5结合 ,而且其结合能力受Zn2 +的影响 .这些结果表明RF1 5可能是PSA启动子中的一个新的附属调节元件 .与之结合的调节蛋白可能是通过与雄激素受体的相互作用促进雄激素对PSA基因的诱导作用 .Human prostate specific antigen (PSA) gene has been shown to be regulated by androgen, and its androgen response element (ARE) has been located at about -170. To determine whether the androgen inducion of the gene was affected by upstream sequence of ARE, different natural and mutated DNA fragments of PSA promoter were linked to the CAT reporter gene respectively, and different pBLCAT3 PSA plasmids were constructed and used for transfection in human prostatic cancer cell line PC 3. The results indicated that a 15 bp segment of RF15 (-340~-326) could cooperate with ARE in maximal androgen induction significantly. The bandshift assay showed that some nucleic regulatory protein from human prostatic cancer cell line LNcap and PC 3 could bind to RF15 DNA fragment. And the protein ability to bind to RF15 was influenced by Zn 2+ . The results suggested that the RF15 may be a new regulatory sequence in the PSA promoter region. The regulatory protein, which binds to the RF15 sequence, may enhance the androgen induction via interaction with androgen receptor.

关 键 词:前列腺特异抗原 基因 雄激素 启动子 前列腺癌 

分 类 号:R392.11[医药卫生—免疫学] R737.250.2[医药卫生—基础医学]

 

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