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Claudin-1 对他莫昔芬处理的人乳腺癌 MCF-7 细胞的抗凋亡作用。

Anti-apoptotic effect of claudin-1 in tamoxifen-treated human breast cancer MCF-7 cells.

机构信息

Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.

出版信息

BMC Cancer. 2010 Oct 12;10:548. doi: 10.1186/1471-2407-10-548.

DOI:10.1186/1471-2407-10-548
PMID:20937153
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2958956/
Abstract

BACKGROUND

Claudin-1 is a membrane protein of tight junctions, and is associated with the development of various cancers. However, the significance of claudin-1 expression in cancer cells is not well understood. Here, we showed for the first time the anti-apoptotic effect of claudin-1 in human breast cancer MCF-7 cells.

METHODS

Human breast cancer MCF-7 and T47 D cells were treated with or without tamoxifen, siRNA against claudin-1, or tamoxifen and claudin-1 siRNA. The samples were analyzed by RT-PCR, Western blotting or immunofluorescent staining.

RESULTS

The expression of claudin-1 was upregulated in tamoxifen-treated MCF-7 cells, whereas the expression of claudin-1 was not altered in tamoxifen-treated T47 D cells. Knockdown of claudin-1 by siRNA increased the amount of poly (ADP-ribose) polymerase (PARP) regardless of tamoxifen treatment in MCF-7 cells, but not T47 D cells. In the cell membranes of the MCF-7 cells, tamoxifen treatment increased the amount of claudin-1, but decreased the amount of β-catenin. Claudin-1 siRNA increased the amount of E-cadherin in the cytoplasm of the MCF-7 cells as well as the amount of β-catenin in their cell membranes.

CONCLUSION

These results indicate that claudin-1 has anti-apoptotic effects, and is involved in the regulation of the expression and subcellular localization of β-catenin and E-cadherin in MCF-7, but not T47 D cells.

摘要

背景

Claudin-1 是紧密连接的膜蛋白，与多种癌症的发生发展有关。然而，Claudin-1 在癌细胞中的表达意义尚不清楚。在这里，我们首次展示了 Claudin-1 在人乳腺癌 MCF-7 细胞中的抗凋亡作用。

方法

用或不用他莫昔芬、Claudin-1 的 siRNA 或他莫昔芬和 Claudin-1 siRNA 处理人乳腺癌 MCF-7 和 T47 D 细胞。通过 RT-PCR、Western blot 或免疫荧光染色分析样品。

结果

Claudin-1 的表达在他莫昔芬处理的 MCF-7 细胞中上调，而 Claudin-1 的表达在他莫昔芬处理的 T47 D 细胞中没有改变。siRNA 敲低 Claudin-1 增加了多聚（ADP-核糖）聚合酶（PARP）的量，而不管 MCF-7 细胞中是否存在他莫昔芬处理，但在 T47 D 细胞中没有。在 MCF-7 细胞的细胞膜中，他莫昔芬处理增加了 Claudin-1 的量，而减少了β-连环蛋白的量。Claudin-1 siRNA 增加了 MCF-7 细胞细胞质中 E-钙粘蛋白的量以及其细胞膜中β-连环蛋白的量。

结论

这些结果表明 Claudin-1 具有抗凋亡作用，并参与调节 MCF-7 中β-连环蛋白和 E-钙粘蛋白的表达和亚细胞定位，但不参与 T47 D 细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e330/2958956/81d8b76b98fb/1471-2407-10-548-8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e330/2958956/4f9518ace274/1471-2407-10-548-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e330/2958956/f8ac91fa885e/1471-2407-10-548-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e330/2958956/9f0a21790cfd/1471-2407-10-548-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e330/2958956/42d6c0629905/1471-2407-10-548-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e330/2958956/369ba000bed2/1471-2407-10-548-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e330/2958956/07b4ab1813fe/1471-2407-10-548-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e330/2958956/789b50d49bfa/1471-2407-10-548-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e330/2958956/81d8b76b98fb/1471-2407-10-548-8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e330/2958956/4f9518ace274/1471-2407-10-548-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e330/2958956/f8ac91fa885e/1471-2407-10-548-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e330/2958956/9f0a21790cfd/1471-2407-10-548-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e330/2958956/42d6c0629905/1471-2407-10-548-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e330/2958956/369ba000bed2/1471-2407-10-548-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e330/2958956/07b4ab1813fe/1471-2407-10-548-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e330/2958956/789b50d49bfa/1471-2407-10-548-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e330/2958956/81d8b76b98fb/1471-2407-10-548-8.jpg

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