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Horm Metab Res 2005; 37(10): 593-601
DOI: 10.1055/s-2005-870525
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Bone Microenvironment-related Growth Factors, Zoledronic Acid and Dexamethasone Differentially Modulate PTHrP Expression in PC-3 Prostate Cancer Cells

R.  Tenta1 , A.  Sourla1 , P.  Lembessis1 , V.  Luu-The2 , M.  Koutsilieris1
  • 1Department of Experimental Physiology, Medical School, University of Athens, Greece
  • 2Endocrine-Oncology Laboratory, Research Centre, Centre Hospitalier Universitaire Laval (CHUL-CHUQ), Quebec, Canada
Further Information

Publication History

Received 4 January 2005

Accepted after revision 25 April 2005

Publication Date:
08 November 2005 (online)

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Abstract

Bone metastasis microenvironment-related growth factors such as insulin-like growth factor 1 (IGF-1), transforming growth factor beta 1 (TGF-β1), 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-β1, 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-β1, bFGF and IL-6 increase PTHrP mRNA expression and its perinuclear localization, while zoledronic acid (50 μM, 100 μM 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- β1, 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.

Key words

PTHrP - PC-3 cell - Bone-derived growth factors - Zoledronic acid

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Michael Koutsilieris, M. D., Ph. D

Department of Experimental Physiology

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