Xu L L, Su Y P, Labiche R, Segawa T, Shanmugam N, McLeod D G, Moul J W, Srivastava S
Center for Prostate Disease Research (CPDR), Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Int J Cancer. 2001 May 1;92(3):322-8. doi: 10.1002/ijc.1196.
Quantitative expression profile of androgen-regulated genes (ARGs) was evaluated in the hormone-responsive prostate cancer cell line LNCaP by serial analysis of gene expression (SAGE). A total of 83,489 SAGE tags representing 23,448 known genes or expressed sequence tags (ESTs) and 1,655 potentially novel sequences have unraveled the transcriptome of LNCaP cells, the most common cell line used in prostate cancer research. Comparison of transcripts between control and R1881-treated LNCaP cells revealed the induction of 136 genes and repression of 215 genes in response to androgen (p < 0.05). Strikingly, a high fraction ( approximately 90%) of ARGs identified in our study has not been described as ARGs previously. A number of prostate-specific transcription factors were among the ARGs identified here. Classification of the ARGs on the basis of biochemical functions revealed that a great majority of ARGs identified in our experimental system appear to be involved in regulation of transcription, splicing, ribosomal biogenesis, mitogenesis, bioenergetics and redox processes. One of the novel aspects of androgen signaling included androgen regulation of genes involved in DNA repair/recombination process. By comparing our LNCaP-C and LNCaP-T SAGE libraries with SAGE tag libraries available at the NCBI-SAGE website, we have identified >200 potential prostate specific/abundant transcripts. The discovery of new prostate-specific genes and ARGs provides a unique opportunity to determine the role of these genes in prostate cell growth, differentiation and tumorigenesis.
通过基因表达序列分析（SAGE）对激素反应性前列腺癌细胞系LNCaP中雄激素调节基因（ARG）的定量表达谱进行了评估。总共83,489个SAGE标签代表了23,448个已知基因或表达序列标签（EST）以及1,655个潜在的新序列，揭示了LNCaP细胞的转录组，这是前列腺癌研究中最常用的细胞系。对照和R1881处理的LNCaP细胞之间的转录本比较显示，雄激素诱导了136个基因，抑制了215个基因（p < 0.05）。引人注目的是，我们研究中鉴定出的很大一部分（约90%）ARG以前未被描述为ARG。这里鉴定出的ARG中有许多是前列腺特异性转录因子。根据生化功能对ARG进行分类表明，在我们的实验系统中鉴定出的绝大多数ARG似乎参与转录、剪接、核糖体生物发生、有丝分裂、生物能量学和氧化还原过程的调节。雄激素信号传导的一个新方面包括雄激素对参与DNA修复/重组过程的基因的调节。通过将我们的LNCaP-C和LNCaP-T SAGE文库与NCBI-SAGE网站上可用的SAGE标签文库进行比较，我们鉴定出了>200个潜在的前列腺特异性/丰富转录本。新的前列腺特异性基因和ARG的发现为确定这些基因在前列腺细胞生长、分化和肿瘤发生中的作用提供了独特的机会。
