TYRO3 as a potential therapeutic target in breast cancer

Anticancer Res. 2014 Jul;34(7):3337-45.

Abstract

Aim: We evaluated the potential of TYRO3 as a therapeutic target in various types of breast cancer cell lines.

Materials and methods: The effects of TYRO3-knockdown by small interfering RNA (siRNA) on proliferation, cell-cycle distribution, and cell signaling in four estrogen receptor (ER)-positive/HER2-non-amplified (luminal-type), two ER-negative/HER2-amplified (HER2-type), and two ER-negative/HER2-non-amplified (triple negative [TN]-type) cell lines were compared.

Results: Whereas TYRO3 knockdown induced the greatest proliferation suppression in luminal-type cells, and to a lesser extent in HER2-type cells, no proliferation inhibition was observed in TN-type cells. The TYRO3 siRNA-induced proliferation inhibition in luminal-type cells was observed in both estradiol (E2)-rich and -null conditions. The proliferation suppression was correlated with G0-G1/S cell-cycle arrest. Western blot analysis showed a decrease in phosphorylation of ERK1/2 or STAT3, and in cyclin D1 only in cell lines sensitive to TYRO3-knockdown.

Conclusion: TYRO3 is a potential therapeutic target in breast cancer, particularly in luminal-type cells.

Keywords: Breast cancer; TYRO3; luminal-type; siRNA; targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / therapy*
  • Cell Cycle / genetics
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Female
  • Gene Knockdown Techniques
  • Humans
  • MCF-7 Cells
  • Molecular Targeted Therapy
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Transfection
  • Triple Negative Breast Neoplasms / enzymology
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / therapy

Substances

  • RNA, Small Interfering
  • Receptor Protein-Tyrosine Kinases
  • TYRO3 protein, human