Clusterin overexpression in both malignant and nonmalignant prostate epithelial cells induces cell cycle arrest and apoptosis

M Scaltriti, S Bettuzzi, R M Sharrard, A Caporali, A E Caccamo, N J Maitland

Research output: Contribution to journalArticlepeer-review

Abstract

Expression of the castration-induced clusterin protein is incompatible with the survival of human prostate cancer cells in tissues and in cell culture. To investigate the fate of human prostate epithelial cells, when engineered to maintain expression of clusterin protein, we have used an IRES-hyg vector and hygromycin selection. PC-3 prostate tumour cells were substantially more sensitive to clusterin expression than nonmalignant PNT1a cells, showing multiple phenotypic changes including cell cycle arrest and increased apoptosis. The results strengthen the hypothesis that clusterin expression is proapoptotic. Expression of exogenous clusterin in both cell types resulted in its relocation from the cytoplasm and a nuclear accumulation of the protein, as was also seen in the same cells when apoptosis was induced by etoposide treatment. To survive clusterin expression, the PC-3 tumour cells developed apoptosis-inhibitory properties. This could have significance for the resistance of prostate cancers to chemo/radiotherapy, where clusterin overexpression is observed.
Original languageEnglish
Pages (from-to)1842-50
Number of pages9
JournalBritish Journal of Cancer
Volume91
Issue number10
DOIs
Publication statusPublished - 15 Nov 2004

Keywords

  • Apoptosis
  • Cell Cycle
  • Cell Line, Transformed
  • Cell Proliferation
  • Clone Cells
  • Clusterin
  • Epithelial Cells
  • Glycoproteins
  • Humans
  • Male
  • Molecular Chaperones
  • Neoplasms, Hormone-Dependent
  • Prostate
  • Prostatic Neoplasms
  • Transfection
  • Tumor Cells, Cultured

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