Bone microenvironment-related growth factors, zoledronic acid and dexamethasone differentially modulate PTHrP expression in PC-3 prostate cancer cells.
Bone metastasis microenvironment-related growth factors such as insulin-like growth factor 1 (IGF-1), transforming growth factor beta 1 (TGF-beta1), basic fibroblast growth factor (bFGF) and interleukin 6 (IL-6) show survival factor activity, thereby inhibiting chemotherapy-induced apoptosis of PC-3 prostate cancer cells in vitro. Recently, zoledronic acid has been shown to induce apoptosis in PC-3 prostate cancer cells while overexpression of parathyroid hormone-related protein (PTHrP) inhibits serum deprivation-induced apoptosis in PC-3 cells. Consequently, we have investigated whether IGF-1, TGF-beta1, bFGF, IL-6, zoledronic acid and/or dexamethasone affect the expression of the PTHrP and type I PTH/PTHrP receptor (PTH.1R) in PC-3 prostate cancer cells using relative quantitative PCR and real-time PCR (expression at mRNA level) and immunocytochemical and immunofluorescence analysis (expression at protein level). Our data show that IGF-1, TGF-beta1, bFGF and IL-6 increase PTHrP mRNA expression and its perinuclear localization, while zoledronic acid (50 muM, 100 muM for 24 h and 48 h) and dexamethasone suppress PTHrP expression in PC-3 cells. We did not detect any appreciable change of the PTH.1R expression due to IGF-1, TGF- beta1, bFGF, IL-6, zoledronic acid or dexamethasone in PC-3 cells. Therefore, it is conceivable that bone metastasis microenvironment-related survival factor/anti-apoptotic activity and zoledronic acid anticancer action/pro-apoptotic activity on PC-3 cells is mediated, at least in part, by differential modulation of PTHrP expression.
Tenta
R
R
Department of Experimental Physiology, Medical School, University of Athens, Greece.
Sourla
A
A
Lembessis
P
P
Luu-The
V
V
Koutsilieris
M
M
D001842:Bone and Bones / Q000378:metabolism*; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology*; D004164:Diphosphonates / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D044162:Parathyroid Hormone-Related Protein / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000077211:Zoledronic Acid
D004164:Diphosphonates; D006133:Growth Substances; D007093:Imidazoles; D015850:Interleukin-6; D044162:Parathyroid Hormone-Related Protein; D044168:Receptor, Parathyroid Hormone, Type 1; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D000077211:Zoledronic Acid; D003907:Dexamethasone