Overexpression of NOTCH-regulated ankyrin repeat protein is associated with breast cancer cell proliferation

Anticancer Res. 2014 May;34(5):2165-71.

Abstract

Background/aim: NOTCH-regulated ankyrin repeat protein (NRARP) has been implicated in crosstalk between NOTCH and wingless-type mouse mammary tumor virus integration site (WNT) signals during development. Our study aimed to clarify its role in breast cancer cells.

Materials and methods: Public microarray data were used to analyze gene expression in human and rat breast cancer. A short interfering RNA was introduced into MCF7 and T47D human breast cancer cells for NRARP silencing. Gene expression was analyzed by quantitative polymerase chain reaction.

Results: The NRARP transcript was commonly overexpressed in various rat mammary cancer models. In addition, a subset of human breast cancer also expressed high levels of NRARP transcript, which correlated positively with up-regulation of cell proliferation-related genes. Silencing of NRARP suppressed the growth of MCF7 and T47D cells and lowered the expression of cell cycle-related genes in MCF7 cells.

Conclusion: NRARP may stimulate cell proliferation in human breast cancer.

Keywords: NOTCH-regulated ankyrin repeat protein; NRARP; breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ankyrin Repeat / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation*
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism
  • Transcriptome
  • Up-Regulation

Substances

  • Intracellular Signaling Peptides and Proteins
  • NRARP protein, human
  • Neoplasm Proteins
  • Receptors, Notch