Clusterin over-expression modulates proapoptotic and antiproliferative effects of 1,25(OH)2D3 in prostate cancer cells in vitro

B. Shannan, M. Seifert, D. A. Boothman, W. Tilgen, J. Reichrath

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Prostate cancer is the most commonly diagnosed cancer in the majority of western countries. Due to their antiproliferative and proapoptotic activity, vitamin D analogues have been introduced recently as an experimental therapy for prostate cancer. Clusterin (CLU) is a glycoprotein that has two known isoforms generated in human cells. A nuclear form of CLU protein (nCLU) is pro-apoptotic, and a secretory form (sCLU) is pro-survival. In this study, we analyzed whether proapoptotic and antiproliferative effects of 1,25(OH)2D3 on LNCaP prostate cancer cells are modulated by expression of sCLU. Using colony forming assay, we studied the effect of treatment with different doses of 1,25(OH)2D3 (10-6, 10-7, 10-10 M) on proliferation of LNCaP cells that were stable transfected and over-express sCLU (LNT-1) as compared to empty vector-transfected cells (LN/C). We also measured apoptosis using TUNEL assay. sCLU over-expression protected against both antiproliferative (30%) and proapoptotic (15%) effects of 1,25(OH)2D3, although this effect was statistically not significant. In conclusion, our findings demonstrate that expression of sCLU modulates growth regulatory effects of 1,25(OH)2D3 in prostate cancer indicating that CLU interferes with vitamin D signalling pathways.

Original languageEnglish (US)
Pages (from-to)721-725
Number of pages5
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume103
Issue number3-5
DOIs
StatePublished - Mar 1 2007

Keywords

  • 1,25(OH)D
  • Antiproliferative effects
  • Apoptosis
  • Clusterin
  • LNCaP

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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