shRNA 介导的 ZFX 沉默减弱了乳腺癌细胞的增殖。

shRNA-mediated silencing of ZFX attenuated the proliferation of breast cancer cells.

机构信息

Department of Breast Surgery, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022, China,

出版信息

Cancer Chemother Pharmacol. 2014 Mar;73(3):569-76. doi: 10.1007/s00280-014-2379-y. Epub 2014 Jan 22.

DOI:10.1007/s00280-014-2379-y

PMID:24448637

Abstract

PURPOSE

Breast cancer is the cause for highest number of cancer-related death among women worldwide. This study was focused on investigating the role of zinc-finger protein X-linked (ZFX) in human breast cancer.

METHODS

Expression levels of ZFX were analyzed in 99 patients and four breast cancer cell lines. Lentivirus-mediated RNA interference was applied to silence ZFX expression, and the effects of ZFX knockdown on the growth of breast cancer cells were investigated.

RESULTS

The immunohistochemical expression of ZFX was higher in more advanced tumor tissues. ZFX was also overexpressed in multiple breast cancer cell lines. Knockdown of ZFX inhibited cell proliferation and colony formation of MCF-7 and MDA-MB-231 cells. Moreover, ZFX silencing resulted in cell cycle arrest at G0/G1 phase. Depletion of ZFX decreased the phosphorylation level of AKT and increased the phosphorylation level of ERK2 and the expression of cyclin D1, which is involved in cell survival and cell cycle regulation.

CONCLUSIONS

These findings suggest that ZFX plays an important role in breast cancer development and could be a potential therapeutic target for breast cancer.

摘要

目的

乳腺癌是全球女性癌症相关死亡的主要原因。本研究旨在探讨 X 连锁锌指蛋白（ZFX）在人乳腺癌中的作用。

方法

分析了 99 例患者和 4 种乳腺癌细胞系中 ZFX 的表达水平。应用慢病毒介导的 RNA 干扰沉默 ZFX 表达，并研究 ZFX 敲低对乳腺癌细胞生长的影响。

结果

免疫组织化学分析显示，ZFX 的表达在肿瘤组织进展程度更高的部位更高。ZFX 在多种乳腺癌细胞系中也过表达。ZFX 敲低抑制 MCF-7 和 MDA-MB-231 细胞的增殖和集落形成。此外，ZFX 沉默导致细胞周期停滞在 G0/G1 期。ZFX 耗竭降低 AKT 的磷酸化水平，增加 ERK2 的磷酸化水平和细胞周期调节相关蛋白 cyclin D1 的表达。