1. Cross-talk between alpha1D-adrenoceptors and transient receptor potential vanilloid type 1 triggers prostate cancer cell proliferation
- Author
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Maria Beatrice Morelli, Gabriele Mammana, Wilma Quaglia, Matteo Santoni, Valerio Farfariello, Alessandro Bonifazi, Giorgio Santoni, Consuelo Amantini, Daniele Tomassoni, Alessandro Piergentili, Alessandra Filosa, Massimo Nabissi, Angela Gismondi, Claudio Cardinali, Fabio Del Bello, Sonia Liberati, and Lucilla Servi
- Subjects
Transient receptor potential vanilloid type 1 ,Male ,medicine.medical_specialty ,Cancer Research ,Proliferation ,TRPV1 ,Gene Expression ,TRPV Cation Channels ,urologic and male genital diseases ,Prostate cancer ,Transient receptor potential channel ,Norepinephrine ,Internal medicine ,α1D-adrenoceptors ,PC3 cell line ,Cell Line, Tumor ,Receptors, Adrenergic, alpha-1 ,medicine ,Genetics ,Humans ,Receptor ,Ion channel ,Cell Proliferation ,Cell growth ,business.industry ,Prostatic Neoplasms ,medicine.disease ,Protein Transport ,Endocrinology ,Oncology ,Cancer research ,Noradrenaline ,Stem cell ,Signal transduction ,business ,Research Article ,Protein Binding ,Signal Transduction - Abstract
Background There is evidence that calcium (Ca2+) increases the proliferation of human advanced prostate cancer (PCa) cells but the ion channels involved are not fully understood. Here, we investigated the correlation between alpha1D-adrenergic receptor (alpha1D-AR) and the transient receptor potential vanilloid type 1 (TRPV1) expression levels in human PCa tissues and evaluated the ability of alpha1D-AR to cross-talk with TRPV1 in PCa cell lines. Methods The expression of alpha1D-AR and TRPV1 was examined in human PCa tissues by quantitative RT-PCR and in PCa cell lines (DU145, PC3 and LNCaP) by cytofluorimetry. Moreover, alpha1D-AR and TRPV1 colocalization was investigated by confocal microscopy in PCa cell lines and by fluorescence microscopy in benign prostate hyperplasia (BPH) and PCa tissues. Cell proliferation was assessed by BrdU incorporation. Alpha1D-AR/TRPV1 knockdown was obtained using siRNA transfection. Signalling pathways were evaluated by measurement of extracellular acidification rate, Ca2+ flux, IP3 production, western blot and MTT assay. Results The levels of the alpha1D-AR and TRPV1 mRNAs are increased in PCa compared to BPH specimens and a high correlation between alpha1D-AR and TRPV1 expression levels was found. Moreover, alpha1D-AR and TRPV1 are co-expressed in prostate cancer cell lines and specimens. Noradrenaline (NA) induced an alpha1D-AR- and TRPV1-dependent protons release and Ca2+ flux in PC3 cell lines; NA by triggering the activation of phospholipase C (PLC), protein kinase C (PKC) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways stimulated PC3 cell proliferation, that was completely inhibited by clopenphendioxan (WS433) and capsazepine (CPZ) combination or by alpha1D-AR/TRPV1 double knockdown. Conclusions We demonstrate a cross-talk between alpha1D-AR and TRPV1, that is involved in the control of PC3 cell proliferation. These data strongly support for a putative novel pharmacological approach in the treatment of PCa by targeting both alpha1D-AR and TRPV1 channels. Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-921) contains supplementary material, which is available to authorized users.
- Published
- 2014