The autocrine human secreted PDZ domain-containing protein 2 (sPDZD2) induces senescence or quiescence of prostate, breast and liver cancer cells via transcriptional activation of p53

Cancer Lett. 2008 Nov 18;271(1):64-80. doi: 10.1016/j.canlet.2008.05.047. Epub 2008 Jul 17.

Abstract

Tumor suppressive actions of the autocrine human secreted PDZ domain-containing protein 2 (sPDZD2) have been reported, but the mechanisms remain enigmatic. Here, we showed that sPDZD2 induced senescence of prostate cancer DU145 cells, quiescence of breast cancer MCF-7 and liver cancer Hep-G2 cells, via transcriptional activation of mutant or wild-type p53. Furthermore, sPDZD2 sensitized mutant p53-positive DU145 cells and wild-type p53-positive MCF-7 cells to apoptosis induction through genotoxic stress imposed by sub-lethal concentration of hydrogen peroxide. Together, our findings suggest a potential autocrine pathway of p53 activation by transcriptional regulation, and a new approach to reactivate p53 for cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / physiology*
  • Apoptosis
  • Base Sequence
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Adhesion Molecules
  • Cell Line, Tumor
  • Cell Proliferation
  • Cellular Senescence / physiology*
  • DNA Primers
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • Neoplasm Proteins / physiology*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptional Activation / physiology*
  • Tumor Suppressor Protein p53 / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Adhesion Molecules
  • DNA Primers
  • Neoplasm Proteins
  • PDZD2 protein, human
  • Tumor Suppressor Protein p53