Identification and characterization of the novel human prostate cancer-specific PC-1 gene promoter

Human prostate and colon gene-1 (PC-1, also known as PrLZ) is an androgen-regulated, prostate tissue and prostate cancer cells specifically expressed novel gene. The increased expression of PC-1 gene appears to promote prostate cancer cells androgen-dependent (AD) and androgen-independent (AI) growth. To clone and investigate the expression and regulation elements of PC-1 gene may provide insight into the function of PC-1 and develop a new promoter that targets therapeutic genes to the AD and AI prostate cancer cells. The goal of the present study is cloning and characterization of the PC-1 promoter. A series of luciferase constructs that contain various fragments of the PC-1 5′-genomic region were transfected into human prostate cancer cells for promoter transactivation analysis. 5′ deletion analysis identified the −1579bp promoter region was required for the maximal proximal promoter activity; two transcriptional suppression and a positive regulatory region were identified; −4939bp promoter fragment of the PC-1 gene retained the characteristic of prostate cancer-specific expression and exhibited higher transcription activity than PSA-6kb promoter in the medium supplemented with steroid-depleted FBS. An androgen response element (ARE) was located in between −345 and −359bp of the PC-1 5′-untranslated region relative to the translation initiation site. Thus, our studies not only provide molecular basis of PC-1 transcription regulation, but also define a new regulatory sequence that may be used to restrict expression of therapeutic genes to prostate cancer in the prostate cancer gene therapy.