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 Citations (Scopus)

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

Fingerprint

Parathyroid Hormone-Related Protein
Gene expression
Vitamin D
Prostatic Neoplasms
Cells
Gene Expression
Proteins
Cell growth
Epidermal Growth Factor
Down-Regulation
Messenger RNA
Calcitriol
Transcription
Growth
Up-Regulation
Genes
Steroids
Cell Line

Keywords

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

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Regulation of PTH-related protein gene expression by vitamin D in PC-3 prostate cancer cells. / Tovar Sepulveda, Veronica A.; Falzon, Miriam.

In: Molecular and Cellular Endocrinology, Vol. 190, No. 1-2, 25.04.2002, p. 115-124.

Research output: Contribution to journalArticle

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