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正常上皮细胞特异性1基因的结构表征与定位

Structural characterization and mapping of the normal epithelial cell-specific 1 gene.

作者信息

Luo L, Herbrick J A, Scherer S W, Beatty B, Squire J, Diamandis E P

机构信息

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.

出版信息

Biochem Biophys Res Commun. 1998 Jun 29;247(3):580-6. doi: 10.1006/bbrc.1998.8793.

Abstract

The normal epithelial cell-specific 1 (NES1) gene is a recently identified novel serine protease-like gene which is down-regulated during breast cancer progression. The gene product has 34-42% identity with the members of three distinct serine protease families: the trypsin-like family, activators of kringle domain-containing growth factors, and the kallikrein family (X. L. Liu et al., (1996) Cancer Res 56, 3371-3379). Although the cDNA of this gene has been cloned, its genomic structure and chromosomal position are not as yet known. Here, we report the genomic characterization and mapping of the NES1 gene. By subcloning and sequencing a PAC clone containing the complete NES1 gene, we were able to characterize the structure of this gene. The NES1 gene spans 5.5 kb and is composed of five coding exons and one untranslated exon. The positions of the introns were similar to trypsinogen, prostate specific antigen (PSA), and tissue plasminogen activator (TPA). NES1 gene was also localized with somatic cell mapping, radiation hybrid mapping, and fluorescence in situ hybridization techniques to chromosome 19q13.3-q13.4, the same region where the human kallikrein gene family resides. Taken together, our results suggest that the NES1 gene originates from the same ancestor as trypsinogen, PSA, and TPA, but remains in close proximity to PSA.

摘要

正常上皮细胞特异性1(NES1)基因是最近鉴定出的一种新型丝氨酸蛋白酶样基因,在乳腺癌进展过程中表达下调。该基因产物与三个不同丝氨酸蛋白酶家族的成员具有34%-42%的同源性:胰蛋白酶样家族、含kringle结构域生长因子的激活剂家族以及激肽释放酶家族(X.L. Liu等人,(1996年)《癌症研究》56,3371-3379)。尽管该基因的cDNA已被克隆,但其基因组结构和染色体定位尚不清楚。在此,我们报告NES1基因的基因组特征和定位。通过亚克隆和测序一个包含完整NES1基因的PAC克隆,我们能够确定该基因的结构。NES1基因跨度为5.5 kb,由五个编码外显子和一个非翻译外显子组成。内含子的位置与胰蛋白酶原、前列腺特异性抗原(PSA)和组织纤溶酶原激活剂(TPA)相似。NES1基因还通过体细胞定位、辐射杂种定位和荧光原位杂交技术定位到19号染色体q13.3-q13.4区域,该区域也是人类激肽释放酶基因家族所在的区域。综上所述,我们的结果表明NES1基因与胰蛋白酶原、PSA和TPA起源于同一祖先,但仍与PSA紧密相邻。

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