Nuclear T-STAR protein expression correlates with HER2 status, hormone receptor negativity and prolonged recurrence free survival in primary breast cancer and decreased cancer cell growth in vitro

PLoS One. 2013 Jul 29;8(7):e70596. doi: 10.1371/journal.pone.0070596. Print 2013.

Abstract

T-STAR (testis-signal transduction and activation of RNA) is an RNA binding protein, containing an SH3-binding domain and thus potentially playing a role in integration of cell signaling and RNA metabolism. The specific function of T-STAR is unknown and its implication in cancer is poorly characterized. Expression of T-STAR has been reported in human testis, muscle and brain tissues, and is associated with a growth-inhibitory role in immortalized fibroblasts. The aim of this paper was to investigate the functional role of T-STAR through (i) survival analysis of patients with primary invasive breast cancer and (ii) experimental evaluation of the effect of T-STAR on breast cancer cell growth. T-STAR protein expression was analysed by immunohistochemistry (IHC) in tissue microarrays with tumors from 289 patients with primary invasive breast cancer, and correlations to clinicopathological characteristics, recurrence-free and overall survival (RFS and OS) and established tumor markers such as HER2 and ER status were evaluated. In addition, the function of T-STAR was investigated using siRNA-mediated knock-down and overexpression of the gene in six breast cancer cell lines. Of the tumors analysed, 86% showed nuclear T-STAR expression, which was significantly associated with an improved RFS and strongly associated with positive HER2 status and negative hormone receptor status. Furthermore, experimental data showed that overexpression of T-STAR decreased cellular growth while knock-down increased it, as shown both by thymidine incorporation and metabolic activity. In summary, we demonstrate that T-STAR protein expression correlates with an improved RFS in primary breast cancer. This is supported by functional data, indicating that T-STAR regulation is of importance both for breast cancer biology and clinical outcome but future studies are needed to determine a potential role in patient stratification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Female
  • Gene Expression
  • Gene Knockdown Techniques
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Staging
  • Protein Transport
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*

Substances

  • KHDRBS3 protein, human
  • RNA-Binding Proteins
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2

Grants and funding

The study was supported by the Lund Institute of Technology (LTH), Cancerfonden (12/0565) and CREATE Health, a strategic Center for Translational Cancer Research (www.createhealth.lth.se). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.