The claudin gene family: expression in normal and neoplastic tissues.
The claudin gene family: expression in normal and neoplastic tissues.
复制标题
DOI：
10.1186/1471-2407-6-186
复制
发表时间：
2006-07-12
期刊：
影响因子：
3.8
通讯作者：
Morin, Patrice J.
中科院分区：
文献类型：
--
作者：
Hewitt, Kyle J.;Agarwal, Rachana;Morin, Patrice J.
紧密连接蛋白（claudin，CLDN）基因编码在紧密连接形成和功能中重要的蛋白质家族。最近，CLDN基因表达在几种人类癌症中经常改变已经变得很明显。然而，在各种癌症中CLDN表达的确切模式是未知的，因为在少数肿瘤中仅研究了有限数量的CLDN基因。我们从Genbank中鉴定了所有人类CLDN基因，并使用大型公共SAGE数据库确定了266个正常和肿瘤组织中所有21个CLDN的基因表达。使用实时RT-PCR，我们还调查了24个正常和24个肿瘤组织中的13个CLDN基因的子集。我们发现，claudins代表了一个高度相关的蛋白质家族，其中claudin-16和-23与其他蛋白质最不同。从计算机模拟分析和RT-PCR数据，我们发现大多数claudin基因在癌症中出现减少，而CLDN 3、CLDN 4和CLDN 7在几种恶性肿瘤中升高，例如源自胰腺、膀胱、甲状腺、输卵管、卵巢、胃、结肠、乳腺、子宫和前列腺的恶性肿瘤。有趣的是，CLDN 5在血管内皮细胞中高度表达，为抗血管生成治疗提供了可能的靶点。CLDN 18可能是胃癌的生物标志物。我们的研究证实了以前已知的CLDN基因表达模式，并确定了新的CLDN基因表达模式，这可能在几种人类癌症的检测，预后和治疗中具有应用价值。特别地，我们鉴定了表达CLDN 3和CLDN 4的几种恶性肿瘤。这些癌症可能是基于CPE开发的新型疗法的理想候选者，CPE是一种特异性结合claudin-3和claudin-4的毒素。
The claudin (CLDN) genes encode a family of proteins important in tight junction formation and function. Recently, it has become apparent that CLDN gene expression is frequently altered in several human cancers. However, the exact patterns of CLDN expression in various cancers is unknown, as only a limited number of CLDN genes have been investigated in a few tumors. We identified all the human CLDN genes from Genbank and we used the large public SAGE database to ascertain the gene expression of all 21 CLDN in 266 normal and neoplastic tissues. Using real-time RT-PCR, we also surveyed a subset of 13 CLDN genes in 24 normal and 24 neoplastic tissues. We show that claudins represent a family of highly related proteins, with claudin-16, and -23 being the most different from the others. From in silico analysis and RT-PCR data, we find that most claudin genes appear decreased in cancer, while CLDN3, CLDN4, and CLDN7 are elevated in several malignancies such as those originating from the pancreas, bladder, thyroid, fallopian tubes, ovary, stomach, colon, breast, uterus, and the prostate. Interestingly, CLDN5 is highly expressed in vascular endothelial cells, providing a possible target for antiangiogenic therapy. CLDN18 might represent a biomarker for gastric cancer. Our study confirms previously known CLDN gene expression patterns and identifies new ones, which may have applications in the detection, prognosis and therapy of several human cancers. In particular we identify several malignancies that express CLDN3 and CLDN4. These cancers may represent ideal candidates for a novel therapy being developed based on CPE, a toxin that specifically binds claudin-3 and claudin-4.
登录
查看更多内容
影响因子：
29.4
作者：
Michl, P;Buchholz, M;Gress, TM
通讯作者：
Gress, TM
影响因子：
2.7
作者：
Folz, RJ;Nepluev, I
通讯作者：
Nepluev, I
影响因子：
10.7
作者：
SAITOU, N;NEI, M
通讯作者：
NEI, M
影响因子：
4.8
作者：
Katahira, J;Sugiyama, H;Sugimoto, N
通讯作者：
Sugimoto, N
DOI：
10.1073/pnas.152324199
发表时间：
2002-08-20
影响因子：
11.1
作者：
Boon, K;Osório, EC;Riggins, GJ
通讯作者：
Riggins, GJ