Portal de Periódicos da CAPES

Artigo Produção Nacional Revisado por pares

BIBTEX RIS

Down-Regulation of SLC8A1 as a Putative Apoptosis Evasion Mechanism by Modulation of Calcium Levels in Penile Carcinoma

2014; Lippincott Williams & Wilkins; Volume: 194; Issue: 1 Linguagem: Inglês

10.1016/j.juro.2014.11.097

1527-3792

Juan José Augusto Moyano Muñoz, Sandra A. Drigo, Mateus Camargo Barros‐Filho, Fábio Albuquerque Marchi, Cristovam Scapulatempo‐Neto, Gustavo de Souza Pessôa, Gustavo Cardoso Guimarães, José Carlos Souza Trindade Filho, Ademar Lopes, Marco Aurélio Zezzi Arruda, Sílvia Regina Rogatto,

Carcinogens and Genotoxicity Assessment

No AccessJournal of UrologyInvestigative Urology1 Jul 2015Down-Regulation of SLC8A1 as a Putative Apoptosis Evasion Mechanism by Modulation of Calcium Levels in Penile Carcinoma Juan J. Muñoz, Sandra A. Drigo, Mateus C. Barros-Filho, Fábio A. Marchi, Cristovam Scapulatempo-Neto, Gustavo S. Pessoa, Gustavo C. Guimarães, José Carlos S. Trindade Filho, Ademar Lopes, Marco A.Z. Arruda, and Silvia R. Rogatto Juan J. MuñozJuan J. Muñoz , Sandra A. DrigoSandra A. Drigo , Mateus C. Barros-FilhoMateus C. Barros-Filho , Fábio A. MarchiFábio A. Marchi , Cristovam Scapulatempo-NetoCristovam Scapulatempo-Neto , Gustavo S. PessoaGustavo S. Pessoa , Gustavo C. GuimarãesGustavo C. Guimarães , José Carlos S. Trindade FilhoJosé Carlos S. Trindade Filho , Ademar LopesAdemar Lopes , Marco A.Z. ArrudaMarco A.Z. Arruda , and Silvia R. RogattoSilvia R. Rogatto View All Author Informationhttps://doi.org/10.1016/j.juro.2014.11.097AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The SLC8A1 gene, which encodes the Na+/Ca2+ exchanger, has a key role in calcium homeostasis. Our previous gene expression oligoarray data revealed SLC8A1 under expression in penile carcinoma. We investigated whether dysregulation of SLC8A1 expression is associated with apoptosis and cell proliferation in penile carcinoma via modulation of the calcium concentration. The underlying mechanisms of SLC8A1 under expression were also explored, focusing on copy number alteration and miRNA. Materials and Methods: Transcript levels of the SLC8A1 gene and miR-223 were evaluated by quantitative polymerase chain reaction to compare penile carcinoma samples with normal glans tissue. SLC8A1 copy number was evaluated by microarray based comparative genomic hybridization. In normal and tumor samples we investigated caspase-3 and Ki-67 immunostaining as well as calcium distribution by laser ablation imaging inductively coupled plasma mass spectrometry. Results: SLC8A1 under expression was detected in penile carcinoma samples (p = 0.001), confirming our previous data. It was not associated with gene copy number loss. In contrast, miR-223 over expression (p = 0.002) inversely correlated with its putative repressor SLC8A1 (r = –0.426, p = 0.015). SLC8A1 under expression was associated with decreased calcium distribution, high Ki-67 and low caspase-3 immunoexpression in penile carcinoma compared to normal tissue. Conclusions: Down-regulation of the SLC8A1 gene, most likely mediated by its regulator miR-223, can lead to decreased calcium in penile carcinoma and consequently to suppressed apoptosis and increased tumor cell proliferation. These data suggest that the miR-223-NCX1-calcium signaling axis may represent a potential therapeutic approach to penile carcinoma. References 1 : Advances in the pathology of penile carcinomas. Hum Pathol2012; 43: 771. Google Scholar 2 : Penile cancer: epidemiology and treatment. Curr Oncol Rep2011; 13: 231. Google Scholar 3 : Penile carcinoma: risk factors and molecular alterations. ScientificWorldJournal2011; 11: 269. Google Scholar 4 : Penile cancer and phallus preservation strategies: a review of current literature. BJU Int2013; 112: 21. Google Scholar 5 : Epigenetic mechanisms in penile carcinoma. Int J Mol Sci2013; 14: 10791. Google Scholar 6 : The ABCs of membrane transporters in health and disease (SLC series): introduction. Mol Aspects Med2013; 34: 95. Google Scholar 7 : Analysis and update of the human solute carrier (SLC) gene superfamily. Hum Genomics2009; 3: 195. Google Scholar 8 : The SLC8 gene family of sodium-calcium exchangers (NCX)—structure, function, and regulation in health and disease. Mol Aspects Med2013; 34: 220. Google Scholar 9 : Ca2+ signalling checkpoints in cancer: remodelling Ca2+ for cancer cell proliferation and survival. Nat Rev Cancer2008; 8: 361. Google Scholar 10 : Calcium channels and pumps in cancer: changes and consequences. J Biol Chem2012; 287: 31666. Google Scholar 11 : Calcium and cancer: targeting Ca2+ transport. Nat Rev Cancer2007; 7: 519. Google Scholar 12 : Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon: IARC Press2004. Google Scholar 13 : TNM Classification of Malignant Tumours, 7th ed. UICC International Union Against Cancer. Chichester: Wiley-Blackwell2009: p 239. Google Scholar 14 : ATM down-regulation is associated with poor prognosis in sporadic breast carcinomas. Ann Oncol2014; 25: 69. Google Scholar 15 : Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol2002; 3. RESEARCH0034. Google Scholar 16 : A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res2001; 29: e45. Google Scholar 17 : Solute carriers (SLCs) in cancer. Mol Aspects Med2013; 34: 719. Google Scholar 18 : Sodium-calcium exchangers (NCX): molecular hallmarks underlying the tissue-specific and systemic functions. Pflugers Arch2014; 466: 43. Google Scholar 19 : Change in intracellular pH causes the toxic Ca2+ entry via NCX1 in neuron- and glia-derived cells. Cell Mol Neurobiol2010; 30: 453. Google Scholar 20 : Laser ablation ICP-MS for quantitative biomedical applications. Anal Bioanal Chem2012; 403: 2113. Google Scholar 21 : Novel bioimaging techniques of metals by laser ablation inductively coupled plasma mass spectrometry for diagnosis of fibrotic and cirrhotic liver disorders. PLoS One2013; 8: e58702. Google Scholar 22 : Laser ablation (imaging) for mapping and determining Se and S in sunflower leaves. Metallomics2013; 5: 62. Google Scholar 23 : Using laser ablation/inductively coupled plasma mass spectrometry to bioimage multiple elements in mouse tumors after hyperthermia. Anal Bioanal Chem2011; 401: 909. Google Scholar 24 : Bioimaging mass spectrometry of trace elements—recent advance and applications of LA-ICP-MS: a review. Anal Chim Acta2014; 835: 1. Google Scholar 25 : Remodeling of calcium signaling in tumor progression. J Biomed Sci2013; 20: 23. Google Scholar 26 : MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol Med2014; 20: 460. Google Scholar 27 : MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca2⁺ overload and cell death. J Clin Invest2012; 122: 1222. Google Scholar 28 : MicroRNAs that target Ca(2+) transporters are involved in vascular smooth muscle cell calcification. Lab Invest2012; 92: 1250. Google Scholar 29 : Drug transporter expression profiling in chemoresistant variants of the A2780 ovarian cancer cell line. Biomed Pharmacother2014; 68: 447. Google Scholar 30 : Sodium/calcium exchanger is upregulated by sulfide signaling, forms complex with the β1 and β3 but not β2 adrenergic receptors, and induces apoptosis. Pflugers Arch2014; 466: 1329. Google Scholar © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byHartz J, Engelmann D, Fürst K, Marquardt S, Spitschak A, Goody D, Protzel C, Hakenberg O and Pützer B (2016) Integrated Loss of miR-1/miR-101/miR-204 Discriminates Metastatic from Nonmetastatic Penile Carcinomas and Can Predict Patient OutcomeJournal of Urology, VOL. 196, NO. 2, (570-578), Online publication date: 1-Aug-2016.Andersson K (2015) This Month in Investigative UrologyJournal of Urology, VOL. 194, NO. 1, (6-7), Online publication date: 1-Jul-2015. Volume 194Issue 1July 2015Page: 245-251Supplementary Materials Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.KeywordscalciumMIRN223 microRNAhumanpenissodium-calcium exchanger 1carcinomaAcknowledgmentsDrs. Maria A. Custódio Domingues and José Vassalo assisted with scientific discussion and immunohistochemistry assays.MetricsAuthor Information Juan J. Muñoz Equal study contribution. More articles by this author Sandra A. Drigo Equal study contribution. More articles by this author Mateus C. Barros-Filho More articles by this author Fábio A. Marchi More articles by this author Cristovam Scapulatempo-Neto More articles by this author Gustavo S. Pessoa More articles by this author Gustavo C. Guimarães More articles by this author José Carlos S. Trindade Filho More articles by this author Ademar Lopes More articles by this author Marco A.Z. Arruda More articles by this author Silvia R. Rogatto More articles by this author Expand All Advertisement PDF downloadLoading ...