Regulation of PTH-related protein gene expression by vitamin D in PC-3 prostate cancer cells

Veronica A. Tovar Sepulveda, Miriam Falzon

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Parathyroid hormone-related protein (PTHrP) is expressed by prostate cancer cells. Since PTHrP increases prostate cancer cell growth and enhances the osteolytic effects of prostate cancer cells, it is important to control PTHrP expression in prostate cancer. Vitamin D exerts a protective effect against prostate cancer through its antiproliferative actions. We investigated whether this steroid also downregulates PTHrP gene transcription, using the human prostate cancer cell line PC-3 as a model system. We report that PTHrP mRNA and secreted protein levels are downregulated by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) via a transcriptional mechanism. We also show that PTHrP gene expression is upregulated, also via a transcriptional mechanism, by epidermal growth factor (EGF), which is normally secreted by prostate cancer cells. 1,25(OH)2D3 reversed the EGF-induced PTHrP upregulation at both the mRNA and protein levels. Since PTHrP enhances prostate cancer cell growth, this study demonstrates the importance of maintaining adequate levels of 1,25(OH)2D3.

Original languageEnglish (US)
Pages (from-to)115-124
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume190
Issue number1-2
DOIs
StatePublished - Apr 25 2002

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Keywords

  • 1,25-Dihydroxyvitamin D
  • Epidermal growth factor
  • Gene regulation
  • PC-3 (prostate cancer cells)
  • Parathyroid hormone-related protein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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