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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Ductal, Breast / therapy
  • Cell Cycle Checkpoints
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Female
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Kruppel-Like Transcription Factors / biosynthesis
  • Kruppel-Like Transcription Factors / deficiency*
  • Kruppel-Like Transcription Factors / genetics*
  • MCF-7 Cells
  • Middle Aged
  • Molecular Targeted Therapy
  • RNA Interference
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics
  • Transfection

Substances

  • Kruppel-Like Transcription Factors
  • RNA, Small Interfering
  • zinc finger protein, X-linked