Paired box 5 is a novel marker of breast cancers that is frequently downregulated by methylation

Int J Biol Sci. 2018 Sep 7;14(12):1686-1695. doi: 10.7150/ijbs.27599. eCollection 2018.

Abstract

Identifying markers for breast cancer is important for both diagnosis and the design of treatment strategies. Recent studies have implicated Paired box 5 (PAX5) as a suppressor in various cancer types, where it is silenced by hypermethylation. However, determining the role of PAX5 in breast cancer requires further study, and the relationship between PAX5 methylation and breast cancer remains unclear. In this study, we found that PAX5 expression was frequently silenced or reduced by methylation in breast cancer cell lines as well as in breast cancer tissues. Restoring expression of PAX5 in breast cancer cells led to tumor suppression through inhibited proliferation and invasion, which resulted from modulation of the cell cycle and altered vascular endothelial growth factor (VEGF) expression. Most importantly, we found that PAX5 methylation status in breast cancer tissues was significantly correlated with patients' age, estrogen receptor (ER) status, progesterone receptor (PR) status, indicating that PAX5 could serve as a marker for breast cancer diagnosis and treatment strategy design.

Keywords: Breast cancer; PAX5; biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Aza Compounds / pharmacology
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • DNA Methylation / drug effects
  • DNA Methylation / genetics
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Hydroxamic Acids / pharmacology
  • MCF-7 Cells
  • Mice
  • PAX5 Transcription Factor / genetics
  • PAX5 Transcription Factor / metabolism*
  • Promoter Regions, Genetic / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Wound Healing / drug effects
  • Wound Healing / genetics

Substances

  • Aza Compounds
  • Biomarkers, Tumor
  • Hydroxamic Acids
  • PAX5 Transcription Factor
  • PAX5 protein, human
  • trichostatin A