Larsen M, Ressler S J, Gerdes M J, Lu B, Byron M, Lawrence J B, Rowley D R
Cell and Molecular Biology Program, Baylor College of Medicine, Houston, Texas 77030, USA.
Mamm Genome. 2000 Sep;11(9):767-73. doi: 10.1007/s003350010135.
We previously identified ps20 protein as a secreted growth inhibitor and purified the protein from fetal rat prostate urogenital sinus mesenchymal cell conditioned medium. The rat cDNA was subsequently cloned, and ps20 was found to contain a WAP-type four-disulfide core motif, indicating it may function as a protease inhibitor. We now report cloning and characterization of the mouse ps20 gene (designated Wfdc1), the human homolog cDNA, and the human gene (designated WFDC1). Both the mouse and human WFDC1 genes consist of seven exons and encode respective ps20 proteins sharing 79.1% identity and nearly identical WAP motifs in exon 2. The WFDC1 gene was mapped by FISH analysis to human Chromosome (Chr) 16q24, an area of frequent loss of heterozygosity (LOH) previously identified in multiple cancers including prostate, breast, hepatocellular, and Wilms' tumor. Identification and characterization of the WFDC1 gene may aid in better understanding the potential role of this gene and ps20 in prostate biology and carcinogenesis.
我们之前将ps20蛋白鉴定为一种分泌性生长抑制剂，并从胎鼠前列腺泌尿生殖窦间充质细胞条件培养基中纯化了该蛋白。随后克隆了大鼠cDNA，发现ps20含有一个WAP型四二硫键核心基序，表明它可能作为一种蛋白酶抑制剂发挥作用。我们现在报告小鼠ps20基因（命名为Wfdc1）、人同源cDNA和人基因（命名为WFDC1）的克隆及特征。小鼠和人WFDC1基因均由七个外显子组成，并编码各自的ps20蛋白，它们在第2外显子中具有79.1%的同一性以及几乎相同的WAP基序。通过荧光原位杂交（FISH）分析将WFDC1基因定位到人类染色体（Chr）16q24，该区域在包括前列腺癌、乳腺癌、肝细胞癌和肾母细胞瘤在内的多种癌症中之前已被鉴定出存在频繁的杂合性缺失（LOH）。WFDC1基因的鉴定和特征分析可能有助于更好地理解该基因和ps20在前列腺生物学和致癌作用中的潜在作用。
