Nelson P S, Ng W L, Schummer M, True L D, Liu A Y, Bumgarner R E, Ferguson C, Dimak A, Hood L
Department of Molecular Biotechnology, University of Washington, Seattle 98195, USA.
Genomics. 1998 Jan 1;47(1):12-25. doi: 10.1006/geno.1997.5035.
The human prostate is a complex glandular organ with functional development under hormonal regulation. Diseases of the prostate result in significant morbidity and mortality in the form of benign prostatic hypertrophy and prostate adenocarcinoma. The characterization of the molecular framework of the human prostate at the level of expressed genes will facilitate the understanding of normal and pathological prostate biology. The purposes of this study were to acquire an initial assessment of the qualitative and quantitative diversity of gene expression in the normal human prostate and to determine the extent that genes with prostate-restricted expression can be assessed using an expressed sequence tag approach. We have constructed a directional cDNA library from normal adult human prostate tissue and partially sequenced the 5' end of 1168 randomly selected cDNA clones, resulting in more than 400 kb of DNA sequence. Homology searches of the sequenced cDNAs against the GenBank and dbEST databases revealed that 43% of the sequences are identical to human genes whose functions are known, 5% are similar but not identical to known genes in humans or lower organisms, 5% match the mitochondrial genome, 9% are composed of interspersed DNA repeats, 30% are homologous to sequences in the dbEST database without a described function, and 6% are novel sequences. A total of 780 distinct species were identified. In addition to the 74 novel transcripts, 4 genes, prostate-specific antigen (PSA), prostate secretory protein (PSP), prostate acid phosphatase (PAP), and human glandular kallekrein 2 (HK2), have no homologous sequences in the databases that originate from sources other than prostate and thus may represent genes with prostate-restricted expression. Sequences matching PSA, PSP, and PAP each accounted for > 1% of the total ESTs and represent highly abundant transcripts, correlating with the abundance of these proteins in the prostate gland. No novel transcripts were represented by more than one EST and thus are expressed at levels much lower than the known prostate-specific genes.
人类前列腺是一个复杂的腺器官，其功能发育受激素调节。前列腺疾病以良性前列腺增生和前列腺腺癌的形式导致显著的发病率和死亡率。在表达基因水平上对人类前列腺分子框架的表征将有助于理解正常和病理前列腺生物学。本研究的目的是对正常人类前列腺中基因表达的定性和定量多样性进行初步评估，并确定使用表达序列标签方法评估前列腺限制性表达基因的程度。我们从正常成人人类前列腺组织构建了一个定向cDNA文库，并对1168个随机选择的cDNA克隆的5'端进行了部分测序，产生了超过400 kb的DNA序列。将测序的cDNA与GenBank和dbEST数据库进行同源性搜索，结果显示43%的序列与功能已知的人类基因相同，5%与人类或低等生物中的已知基因相似但不完全相同，5%与线粒体基因组匹配，9%由散布的DNA重复序列组成，30%与dbEST数据库中未描述功能的序列同源，6%是新序列。总共鉴定出780个不同的物种。除了74个新转录本外，4个基因，前列腺特异性抗原（PSA）、前列腺分泌蛋白（PSP）、前列腺酸性磷酸酶（PAP）和人腺激肽释放酶2（HK2），在数据库中没有来自前列腺以外来源的同源序列，因此可能代表前列腺限制性表达的基因。与PSA、PSP和PAP匹配的序列各自占总ESTs的>1%，代表高度丰富的转录本，与这些蛋白质在前列腺中的丰度相关。没有新转录本由多个EST代表，因此其表达水平远低于已知的前列腺特异性基因。
