Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore, Maryland, United States of America.
PLoS One. 2011;6(7):e22119. doi: 10.1371/journal.pone.0022119. Epub 2011 Jul 15.
Claudins are tight junction proteins that are involved in tight junction formation and function. Previous studies have shown that claudin-7 is frequently upregulated in epithelial ovarian cancer (EOC) along with claudin-3 and claudin-4. Here, we investigate in detail the expression patterns of claudin-7, as well as its possible functions in EOC.
METHODOLOGY/PRINCIPAL FINDINGS: A total of 95 ovarian tissue samples (7 normal ovarian tissues, 65 serous carcinomas, 11 clear cell carcinomas, 8 endometrioid carcinomas and 4 mucinous carcinomas) were studied for claudin-7 expression. In real-time RT-PCR analysis, the gene for claudin-7, CLDN7, was found to be upregulated in all the tumor tissue samples studied. Similarly, immunohistochemical analysis and western blotting showed that claudin-7 protein was significantly overexpressed in the vast majority of EOCs. Small interfering RNA-mediated knockdown of claudin-7 in ovarian cancer cells led to significant changes in gene expression as measured by microarrays and validated by RT-PCR and immunoblotting. Analyses of the genes differentially expressed revealed that the genes altered in response to claudin-7 knockdown were associated with pathways implicated in various molecular and cellular functions such as cell cycle, cellular growth and proliferation, cell death, development, and cell movement. Through functional experiments in vitro, we found that both migration and invasion were altered in cells where CLDN7 had been knocked down or overexpressed. Interestingly, claudin-7 expression was associated with a net increase in invasion, but also with a decrease in migration.
CONCLUSION/SIGNIFICANCE: Our work shows that claudin-7 is significantly upregulated in EOC and that it may be functionally involved in ovarian carcinoma invasion. CLDN7 may therefore represent potential marker for ovarian cancer detection and a target for therapy.
紧密连接蛋白 Claudin-7 与 Claudin-3 和 Claudin-4 一起在卵巢上皮性癌（EOC）中频繁上调。本研究旨在详细研究 Claudin-7 的表达模式及其在 EOC 中的可能作用。
方法/主要发现：共研究了 95 例卵巢组织样本（7 例正常卵巢组织、65 例浆液性癌、11 例透明细胞癌、8 例子宫内膜样癌和 4 例黏液性癌） Claudin-7 的表达。实时 RT-PCR 分析显示，研究的所有肿瘤组织样本中 Claudin-7 基因均上调。同样，免疫组化分析和 Western blot 显示 Claudin-7 蛋白在绝大多数 EOC 中显著过表达。卵巢癌细胞中 Claudin-7 的小干扰 RNA 介导敲低导致基因表达发生显著变化，通过微阵列分析，并通过 RT-PCR 和免疫印迹验证。差异表达基因分析显示，对 Claudin-7 敲低反应的基因与参与各种分子和细胞功能的途径相关，如细胞周期、细胞生长和增殖、细胞死亡、发育和细胞运动。通过体外功能实验，我们发现下调或过表达 CLDN7 均可改变细胞的迁移和侵袭能力。有趣的是，Claudin-7 的表达与侵袭的净增加有关，但与迁移的减少有关。
结论/意义：我们的工作表明 Claudin-7 在 EOC 中显著上调，并且可能在卵巢癌侵袭中具有功能作用。CLDN7 可能因此成为卵巢癌检测的潜在标志物和治疗靶点。
