Cross-talk between alpha1D-adrenoceptors and transient receptor potential vanilloid type 1 triggers prostate cancer cell proliferation

被引：37

作者：

Morelli, Maria Beatrice ^{[1
]}

Amantini, Consuelo ^{[2
]}

Nabissi, Massimo ^{[1
]}

Liberati, Sonia ^{[1
,3
]}

Cardinali, Claudio ^{[1
,3
]}

Farfariello, Valerio ^{[1
,4
]}

Tomassoni, Daniele

Quaglia, Wilma ^{[5
]}

Piergentili, Alessandro ^{[5
]}

Bonifazi, Alessandro ^{[5
]}

Del Bello, Fabio ^{[5
]}

Santoni, Matteo ^{[6
]}

Mammana, Gabriele ^{[7
]}

Servi, Lucilla ^{[7
]}

Filosa, Alessandra ^{[8
]}

Gismondi, Angela ^{[3
]}

Santoni, Giorgio ^{[1
]}

机构：

[1] Univ Camerino, Sch Pharm, Sect Expt Med, I-62032 Camerino, Italy

[2] Univ Camerino, Sch Biosci & Vet Med, I-62032 Camerino, Italy

[3] Univ Roma La Sapienza, Dept Mol Med, I-00161 Rome, Italy

[4] Fdn Cenci Bolognetti, Ist Pasteur, I-00161 Rome, Italy

[5] Univ Camerino, Sch Pharm, Med Chem Unit, I-62032 Camerino, Italy

[6] Polytech Univ Marche, AOU Osped Riuniti, Dept Med Oncol, I-60126 Ancona, Italy

[7] ASUR 9, Urol Unit, I-62100 Macerata, Italy

[8] ASUR 9, Pathol Unit, I-62100 Macerata, Italy

来源：

BMC CANCER | 2014年 / 14卷

关键词：

alpha(1D)-adrenoceptors; Transient receptor potential vanilloid type 1; Noradrenaline; Proliferation; PC3 cell line; Prostate cancer; CA2+-PERMEABLE CATIONIC CHANNELS; ALPHA(1)-ADRENOCEPTOR SUBTYPES; ANDROGEN RECEPTOR; ANTAGONIST NAFTOPIDIL; SIGNAL-TRANSDUCTION; GROWTH; EXPRESSION; CA2+; LOCALIZATION; LNCAP;

D O I：

10.1186/1471-2407-14-921

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 alpha(1D) adrenergic receptor (alpha(1D) AR) and the transient receptor potential vanilloid type 1 (TRPV1) expression levels in human PCa tissues and evaluated the ability of alpha(1D)-AR to cross-talk with TRPV1 in PCa cell lines. Methods: The expression of alpha(1D)-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, alpha(1D)-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. Alpha(1D)-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 alpha(1D)-AR and TRPV1 mRNAs are increased in PCa compared to BPH specimens and a high correlation between alpha(1D)-AR and TRPV1 expression levels was found. Moreover, alpha(1D)-AR and TRPV1 are co-expressed in prostate cancer cell lines and specimens. Noradrenaline (NA) induced an alpha(1D)-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 alpha(1D)-AR/TRPV1 double knockdown. Conclusions: We demonstrate a cross-talk between alpha(1D)-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 alpha(1D)-AR and TRPV1 channels.

引用

页数：13

共 42 条

[1] A SIMPLE, SENSITIVE, AND SPECIFIC RADIORECEPTOR ASSAY FOR INOSITOL 1,4,5-TRISPHOSPHATE IN BIOLOGICAL TISSUES [J].