Mizokami A, Chang C
Department of Human Oncology, University of Wisconsin, Madison 53792.
J Biol Chem. 1994 Oct 14;269(41):25655-9.
Androgens and androgen receptor (AR) play important roles in sexual differentiation and prostatic cancer cell proliferation. To investigate the regulation of AR expression, a 2-kilobase pair 5'-flanking region of human AR gene including a 0.6-kilobase pair 5'-untranslated region (5'-UTR) was ligated to a chloramphenicol acetyltransferase (CAT) gene and characterized by CAT assay after transfection into HeLa cells. The results revealed that AR 5'-UTR was absolutely needed for the induction of CAT activity, but could not function as an enhancer for the AR transcription. A further study using a 180 base pairs (+21 to +202 including a stem-loop secondary structure at +109 to +129) within the AR 5'-UTR demonstrated that this region was sufficient to induce more CAT activity without changing the CAT mRNA expression. Taken together, these results strongly suggested that 5'-UTR of AR mRNA plays an essential role in the induction of AR translation, which may represent the first reported translational induction mechanism in the steroid receptor superfamily.
雄激素和雄激素受体（AR）在性别分化和前列腺癌细胞增殖中发挥着重要作用。为了研究AR表达的调控机制，将包含0.6千碱基对5'-非翻译区（5'-UTR）的人类AR基因的2千碱基对5'-侧翼区域连接到氯霉素乙酰转移酶（CAT）基因上，并在转染HeLa细胞后通过CAT测定进行表征。结果表明，AR 5'-UTR对于CAT活性的诱导是绝对必需的，但不能作为AR转录的增强子。使用AR 5'-UTR内的180个碱基对（+21至+202，包括+109至+129处的茎环二级结构）进行的进一步研究表明，该区域足以诱导更多的CAT活性，而不会改变CAT mRNA的表达。综上所述，这些结果强烈表明，AR mRNA的5'-UTR在AR翻译的诱导中起着至关重要的作用，这可能是类固醇受体超家族中首次报道的翻译诱导机制。
