ABSTRACT
Title
HDAC inhibitors induce NIS expression in testicular cells of carcinoma
Authors
V. Maggisano1, M. Celano1, M. D’Agostino1, G. Tamburrano2, A. Verrienti2, MV. Dima2, S. Micali3, G. Isgrò3, G. Sammarco1, M. Sponziello2, C. Durante2, R. Sacco1 and D. Russo1.
1Department of Pharmacobiological Sciences, University of Catanzaro ‘Magna Graecia’, 88100 Catanzaro, Italy;
2Department of Internal Medicine and Medical Specialties, University of Rome "Sapienza" 00161 Rome, Italy;
3Department of Urology, University of Modena and Reggio Emilia, 41100 Modena, Italy.
1Department of Pharmacobiological Sciences, University of Catanzaro ‘Magna Graecia’, 88100 Catanzaro, Italy;
2Department of Internal Medicine and Medical Specialties, University of Rome "Sapienza" 00161 Rome, Italy;
3Department of Urology, University of Modena and Reggio Emilia, 41100 Modena, Italy.
Abstract
Radioiodine (131I) is currently used for therapeutic treatment of thyroid cancer and is actually investigated as a potential therapeutic tool for extra-thyroid tumours able to concentrate this radioisotope. Radioiodide concentration requires the presence and function of the Na+/I- symporter (NIS), a glycoprotein responsible for iodide transport across the basal membrane of the thyrocytes. NIS expression has been demonstrated in normal testicular tissue both at transcript and protein levels.
In this study, we analyzed the regulation of NIS mRNA and protein expression in Leydig (LC-540) and embryonal (NTERA) testicular carcinoma cells in culture by real time RT-PCR and western blotting respectively. NIS mRNA levels were also investigated in 4 embryonal testicular carcinoma (including one mixed embryonal-choriocarcinoma) and 2 Leydig cell cancer.
The cells were treated with the histone deacetylase (HDCA) inhibitors SAHA 0.3 and 3 µM, Valproic Acid 1 and 3mM, the demethylating agent 5-Azacytidine 0.5 µM and Forskolin 10 µM at various incubation time. The strongest stimulating effects were detected with the HDCA inhibitors SAHA 3 µM and Valproic Acid 3 mM at 24 h, with a significant increaseof NISmRNA levels. At the same concentrationswe found an increase of NIS protein expression in NTERA cells. NIS mRNA was detected in 1 Leydig cell tumor and all the embryonal carcinoma examined.
In conclusion, we found that the NIS is expressed in the cells from Leydig cells and embryonal carcinoma of human testis and its expression is positively regulated by HDCA inhibitors. Futher studies are in progress to test wheter such a regulatory action occur also in vivo suggesting theuseof a NIS-targeting radioiodine-based treatment also for these testicular tumors.
In this study, we analyzed the regulation of NIS mRNA and protein expression in Leydig (LC-540) and embryonal (NTERA) testicular carcinoma cells in culture by real time RT-PCR and western blotting respectively. NIS mRNA levels were also investigated in 4 embryonal testicular carcinoma (including one mixed embryonal-choriocarcinoma) and 2 Leydig cell cancer.
The cells were treated with the histone deacetylase (HDCA) inhibitors SAHA 0.3 and 3 µM, Valproic Acid 1 and 3mM, the demethylating agent 5-Azacytidine 0.5 µM and Forskolin 10 µM at various incubation time. The strongest stimulating effects were detected with the HDCA inhibitors SAHA 3 µM and Valproic Acid 3 mM at 24 h, with a significant increaseof NISmRNA levels. At the same concentrationswe found an increase of NIS protein expression in NTERA cells. NIS mRNA was detected in 1 Leydig cell tumor and all the embryonal carcinoma examined.
In conclusion, we found that the NIS is expressed in the cells from Leydig cells and embryonal carcinoma of human testis and its expression is positively regulated by HDCA inhibitors. Futher studies are in progress to test wheter such a regulatory action occur also in vivo suggesting theuseof a NIS-targeting radioiodine-based treatment also for these testicular tumors.