Prostate cancer cell type-specific regulation of the human PTHrP gene via a negative VDRE

Veronica A. Tovar Sepulveda, Miriam Falzon

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Parathyroid hormone-related protein (PTHrP) is expressed by prostate cancer cells. Since PTHrP increases the growth and enhances the osteolytic effects of prostate cancer cells, it is important to control the level of PTHrP expression in these cells. We show that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its non-calcemic analogue, EB1089, suppress PTHrP mRNA and protein levels in the human prostate cancer cell lines PC-3 and LNCaP. The human PTHrP gene contains a sequence element homologous to the negative vitamin D response element within the parathyroid hormone gene. This DNA sequence (nVDREhPTHrP) bound the vitamin D receptor (VDR) present in nuclear extracts from both PC-3 and LNCaP cells. However, when cloned upstream of the SV40 promoter and transiently transfected into PC-3 and LNCaP cells, nVDREhPTHrP downregulated promoter activity in response to 1,25(OH)2D3 or EB1089 treatment in LNCaP, but not in PC-3, cells. These results may help to explain why some prostate cancers appear to be refractory to treatment with vitamin D analogues.

Original languageEnglish (US)
Pages (from-to)51-64
Number of pages14
JournalMolecular and Cellular Endocrinology
Volume204
Issue number1-2
DOIs
StatePublished - Jun 30 2003

Keywords

  • 1,25-Dihydroxyvitamin D
  • EB1089
  • EMSA
  • LNCaP (prostate cancer cells)
  • Negative vitamin D response element
  • PC-3 (prostate cancer cells)
  • Parathyroid hormone-related protein
  • Promoter activity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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