Regulation of PTH-related protein gene expression by vitamin D in PC-3 prostate cancer cells.
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 D(3) (1,25(OH)(2)D(3)) 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)(2)D(3) 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)(2)D(3).
Tovar Sepulveda
Veronica A
VA
Department of Pharmacology and Toxicology and Sealy Center for Molecular Science, University of Texas Medical Branch, 10th and Market Streets, , Galveston 775550 1031, USA.
Falzon
Miriam
M
D000818:Animals; D002117:Calcitriol / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein; D036361:Peptide Hormones / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D036361:Peptide Hormones; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D002117:Calcitriol