| 摘要 |
A DNA sequence (-426 to +28 base pairs) cloned from the probasin (PB) gene promoter region confers androgen regulation in cell culture and prostate specific expression in transgenic non-human eukaryotic animals. Various PB promoter fragments impart preferential regulation by androgens compared to other steroid hormones on fused transgenes. Alteration of the DNA sequences and/or combinations of the sequences offer improvements on the sensitivity of the bioassay for androgenic and anti-androgenic materials where androgenic is defined as any ligand or pathway that leads to the activation of androgen action. This assay also measures the significance of alteration of amino acids in the androgen receptor on its bioactivity or ability to bind to DNA sequences. In transgenic non-human eukaryotic animals, the PB sequence directs fused transgene expression to the prostate which then can control the growth or function of prostatic cells. Expression of any gene specifically in prostatic cells or cells prostate in origin, can change the characteristics of those cells. Animal models for prostatic hyperplasia and prostate cancer can be developed as well as cells isolated from these new animal models can be placed into culture to develop new cell cultures models. Exposure of either animal or culture models to any material can determine effectiveness of therapies on prostatic disease for a cure or relief of symptoms. These same animal or culture models may test any material for carcinogenicity or protection against development of prostatic neoplasms. Further, the ability of PB to target trangenes to prostatic cells permits the targeting of genes to human prostatic cells for the treatment of human benign prostatic hyperplasia and human prostate cancer.
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