Cole K A, Chuaqui R F, Katz K, Pack S, Zhuang Z, Cole C E, Lyne J C, Linehan W M, Liotta L A, Emmert-Buck M R
Laboratory of Pathology, Division of Clinical Sciences, National Cancer Institute, National Institues of Health, Bethesda, Maryland 20892, USA.
Genomics. 1998 Jul 15;51(2):282-7. doi: 10.1006/geno.1998.5359.
We recently identified a novel gene (PB39) (HGMW-approved symbol POV1) whose expression is up-regulated in human prostate cancer using tissue microdissection-based differential display analysis. In the present study we report the full-length sequencing of PB39 cDNA, genomic localization of the PB39 gene, and genomic sequence of the mouse homologue. The full-length human cDNA is 2317 nucleotides in length and contains an open reading frame of 559 amino acids which does not show homology with any reported human genes. The N-terminus contains charged amino acids and a helical loop pattern suggestive of an srp leader sequence for a secreted protein. Fluorescence in situ hybridization using PB39 cDNA as probe mapped the gene to chromosome 11p11.1-p11.2. Comparison of PB39 cDNA sequence with murine sequence available in the public database identified a region of previously sequenced mouse genomic DNA showing 67% amino acid sequence homology with human PB39. Based on alignment and comparison to the human cDNA the mouse genomic sequence suggests there are at least 14 exons in the mouse gene spread over approximately 100 kb of genomic sequence. Further analysis of PB39 expression in human tissues shows the presence of a unique splice variant mRNA that appears to be primarily associated with fetal tissues and tumors. Interestingly, the unique splice variant appears in prostatic intraepithelial neoplasia, a microscopic precursor lesion of prostate cancer. The current data support the hypothesis that PB39 plays a role in the development of human prostate cancer and will be useful in the analysis of the gene product in further human and murine studies.
我们最近通过基于组织显微切割的差异显示分析，鉴定出一个新基因（PB39）（HGMW批准符号POV1），其在人类前列腺癌中的表达上调。在本研究中，我们报告了PB39 cDNA的全长测序、PB39基因的基因组定位以及小鼠同源物的基因组序列。全长人类cDNA长度为2317个核苷酸，包含一个559个氨基酸的开放阅读框，与任何已报道的人类基因均无同源性。N端含有带电荷的氨基酸和螺旋环模式，提示为分泌蛋白的信号肽序列。以PB39 cDNA为探针进行荧光原位杂交，将该基因定位于染色体11p11.1 - p11.2。将PB39 cDNA序列与公共数据库中可用的小鼠序列进行比较，发现一个先前测序的小鼠基因组DNA区域与人类PB39的氨基酸序列同源性为67%。基于与人类cDNA的比对和比较，小鼠基因组序列表明该小鼠基因至少有14个外显子，分布在约100 kb的基因组序列上。对PB39在人类组织中的表达进一步分析显示，存在一种独特的剪接变异体mRNA，似乎主要与胎儿组织和肿瘤相关。有趣的是，这种独特的剪接变异体出现在前列腺上皮内瘤变中，这是前列腺癌的一种微观前体病变。目前的数据支持PB39在人类前列腺癌发生中起作用的假说，并且将有助于在进一步的人类和小鼠研究中分析该基因产物。
