Nek2 as a novel molecular target for the treatment of breast carcinoma

Cancer Sci. 2009 Jan;100(1):111-6. doi: 10.1111/j.1349-7006.2008.01007.x.

Abstract

We investigated the role of Nek2, a member of the serine-threonine kinase family, in the tumorigenic growth of breast carcinoma. Increased expression of Nek2 was observed in all breast carcinoma cell lines examined (BT20, BT474, Hs578T, MCF7, MDA-MB-231, T47D, and ZR-75-1) by immunoblotting. By treatment with Nek2 short interfering RNA (siRNA), expression of Nek2 was clearly decreased in both estrogen receptor (ER)-positive (MCF7) and ER-negative (MDA-MB-231) breast carcinoma cell lines. Cell growth, colony formation in soft agar, and in vitro invasiveness of these cell lines were substantially suppressed by Nek2 siRNA treatment. In a xenograft nude mouse model with subcutaneous implantation of MCF7 or MDA-MB-231, subcutaneous injection of Nek2 siRNA around the tumor nodules resulted in a reduction of tumor size compared with those of control siRNA injection. Taken together, Nek2 appears to play a pivotal role in tumorigenic growth of breast carcinoma cells, and could be a useful therapeutic molecular target for the treatment of breast carcinoma both in ER-positive and ER-negative cases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Cell Line, Tumor
  • Female
  • Humans
  • Male
  • Mice
  • NIMA-Related Kinases
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / physiology
  • RNA, Small Interfering / genetics
  • Receptors, Estrogen / analysis

Substances

  • RNA, Small Interfering
  • Receptors, Estrogen
  • NEK2 protein, human
  • NIMA-Related Kinases
  • Protein Serine-Threonine Kinases