Protein tyrosine phosphatase µ (PTP µ or PTPRM), a negative regulator of proliferation and invasion of breast cancer cells, is associated with disease prognosis

PLoS One. 2012;7(11):e50183. doi: 10.1371/journal.pone.0050183. Epub 2012 Nov 20.

Abstract

Background: PTPRM has been shown to exhibit homophilic binding and confer cell-cell adhesion in cells including epithelial and cancer cells. The present study investigated the expression of PTPRM in breast cancer and the biological impact of PTPRM on breast cancer cells.

Design: Expression of PTPRM protein and gene transcript was examined in a cohort of breast cancer patients. Knockdown of PTPRM in breast cancer cells was performed using a specific anti-PTPRM transgene. The impact of PTPRM knockdown on breast cancer was evaluated using in vitro cell models.

Results: A significant decrease of PTPRM transcripts was seen in poorly differentiated and moderately differentiated tumours compared with well differentiated tumours. Patients with lower expression of PTPRM had shorter survival compared with those which had a higher level of PTPRM expression. Knockdown of PTPRM increased proliferation, adhesion, invasion and migration of breast cancer cells. Furthermore, knockdown of PTPRM in MDA-MB-231 cells resulted in increased cell migration and invasion via regulation of the tyrosine phosphorylation of ERK and JNK.

Conclusions: Decreased expression of PTPRM in breast cancer is correlated with poor prognosis and inversely correlated with disease free survival. PTPRM coordinated cell migration and invasion through the regulation of tyrosine phosphorylation of ERK and JNK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Extracellular Signal-Regulated MAP Kinases / genetics*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • MAP Kinase Kinase 4 / genetics*
  • MAP Kinase Kinase 4 / metabolism
  • Neoplasm Grading
  • Phosphorylation
  • Prognosis
  • RNA, Messenger / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / antagonists & inhibitors
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / genetics*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Survival Analysis

Substances

  • RNA, Messenger
  • Extracellular Signal-Regulated MAP Kinases
  • MAP Kinase Kinase 4
  • PTPRM protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2

Grants and funding

The present study was supported by Cancer Research Wales and Breast Cancer Hope Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.