Lin B, White J T, Ferguson C, Bumgarner R, Friedman C, Trask B, Ellis W, Lange P, Hood L, Nelson P S
Department of Molecular Biotechnology, University of Washington, Seattle 98195, USA.
Cancer Res. 2000 Feb 15;60(4):858-63.
Genes regulated by androgenic hormones are of critical importance for the normal physiological function of the human prostate gland, and they contribute to the development and progression of prostate carcinoma. We used cDNA microarrays containing 1500 prostate-derived cDNAs to profile transcripts regulated by androgens in prostate cancer cells. This study identified a novel gene that we have designated PART-1 (prostate androgen-regulated transcript 1), which exhibited increased expression upon exposure to androgens in the LNCaP prostate cancer cell line. Northern analysis demonstrated that PART-1 is highly expressed in the prostate gland relative to other normal human tissues and is expressed as different transcripts using at least three different polyadenylation signals. The PART-1 cDNA and putative protein are not significantly homologous to any sequences in the nonredundant public sequence databases. Cloning and analysis of the putative PART-1 promoter region identified a potential binding site for the homeobox gene PBX-la, but no consensus androgen response element or sterol-regulatory element binding sites were identified. We used a radiation hybrid panel and fluorescence in situ hybridization to map the PART-1 gene to chromosome 5q12, a region that has been suggested to harbor a prostate tumor suppressor gene. These results identify a new gene involved in the androgen receptor-regulated gene network of the human prostate that may play a role in the etiology of prostate carcinogenesis.
雄激素调节的基因对于人类前列腺的正常生理功能至关重要,并且它们有助于前列腺癌的发生和发展。我们使用包含1500个前列腺来源cDNA的cDNA微阵列来分析前列腺癌细胞中受雄激素调节的转录本。这项研究鉴定出一个新基因,我们将其命名为PART-1(前列腺雄激素调节转录本1),该基因在LNCaP前列腺癌细胞系中暴露于雄激素时表达增加。Northern分析表明,与其他正常人体组织相比,PART-1在前列腺中高表达,并且使用至少三种不同的聚腺苷酸化信号以不同的转录本形式表达。PART-1 cDNA和推测的蛋白质与非冗余公共序列数据库中的任何序列均无明显同源性。对推测的PART-1启动子区域进行克隆和分析,确定了一个同源异型盒基因PBX-1a的潜在结合位点,但未发现共有雄激素反应元件或固醇调节元件结合位点。我们使用辐射杂种细胞系和荧光原位杂交将PART-1基因定位于5q12染色体,该区域被认为含有前列腺肿瘤抑制基因。这些结果鉴定出一个参与人类前列腺雄激素受体调节基因网络的新基因,该基因可能在前列腺癌发生的病因学中起作用。