The CSB repair factor is overexpressed in cancer cells, increases apoptotic resistance, and promotes tumor growth

DNA Repair (Amst). 2013 Apr 1;12(4):293-9. doi: 10.1016/j.dnarep.2013.01.008. Epub 2013 Feb 16.

Abstract

In the present study we show that a number of cancer cell lines from different tissues display dramatically increased expression of the Cockayne Syndrome group B (CSB) protein, a DNA repair factor, that has recently been shown to be involved in cell robustness. Furthermore, we demonstrated that ablation of this protein by antisense technology causes devastating effects on tumor cells through a drastic reduction of cell proliferation and massive induction of apoptosis, while non-transformed cells remain unaffected. Finally, suppression of CSB in cancer cells makes these cells hypersensitive to a variety of commonly used cancer chemotherapeutic agents. Based on these results, we conclude that cancer cells overexpress CSB protein in order to enhance their anti-apoptotic capacity. The fact that CSB suppression specifically affects only cancerous cells, without harming healthy cells, suggests that CSB may be a very attractive target for the development of new anticancer therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Cell Proliferation / drug effects
  • Cell Transformation, Neoplastic / genetics
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism*
  • Gene Expression
  • HeLa Cells
  • Humans
  • MCF-7 Cells
  • Neoplasms / metabolism*
  • Poly-ADP-Ribose Binding Proteins
  • RNA, Small Interfering

Substances

  • Antineoplastic Agents
  • Poly-ADP-Ribose Binding Proteins
  • RNA, Small Interfering
  • DNA Helicases
  • ERCC6 protein, human
  • DNA Repair Enzymes