TY - JOUR
T1 - Regulation of PTH-related protein gene expression by vitamin D in PC-3 prostate cancer cells
AU - Tovar Sepulveda, Veronica A.
AU - Falzon, Miriam
N1 - Funding Information:
We wish to thank Dr Milan Uskokovic, Hoffman La Roche, for supplying 1,25-dihydroxyvitamin D 3 . We also wish to thank Dr D. Konkel, Dr P.K. Seitz, and Dr M.L. Thomas for critical reading of the manuscript. This work was supported by NIH grant CA83940.
PY - 2002/4/25
Y1 - 2002/4/25
N2 - 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.
AB - 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.
KW - 1,25-Dihydroxyvitamin D
KW - Epidermal growth factor
KW - Gene regulation
KW - PC-3 (prostate cancer cells)
KW - Parathyroid hormone-related protein
UR - http://www.scopus.com/inward/record.url?scp=0037171450&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037171450&partnerID=8YFLogxK
U2 - 10.1016/S0303-7207(02)00003-5
DO - 10.1016/S0303-7207(02)00003-5
M3 - Article
C2 - 11997185
AN - SCOPUS:0037171450
SN - 0303-7207
VL - 190
SP - 115
EP - 124
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -