RT Journal Article T1 Methylation alterations are not a major cause of PTTG1 misregulation. A1 Hidalgo, Manuel A1 Galan, Jose Jorge A1 Sáez, Carmen A1 Ferrero, Eduardo A1 Castilla, Carolina A1 Ramirez-Lorca, Reposo A1 Pelaez, Pablo A1 Ruiz, Agustin A1 Japón, Miguel A A1 Royo, Jose Luis K1 Técnicas de Cultivo de Célula K1 Regulación Neoplásica de la Expresión Génica K1 Proteínas de Neoplasias K1 Línea Celular Tumoral K1 Metilación de ADN K1 Epigénesis Genética AB BACKGROUNDOn its physiological cellular context, PTTG1 controls sister chromatid segregation during mitosis. Within its crosstalk to the cellular arrest machinery, relies a checkpoint of integrity for which gained the over name of securin. PTTG1 was found to promote malignant transformation in 3T3 fibroblasts, and further found to be overexpressed in different tumor types. More recently, PTTG1 has been also related to different processes such as DNA repair and found to trans-activate different cellular pathways involving c-myc, bax or p53, among others. PTTG1 over-expression has been correlated to a worse prognosis in thyroid, lung, colorectal cancer patients, and it can not be excluded that this effect may also occur in other tumor types. Despite the clinical relevance and the increasing molecular characterization of PTTG1, the reason for its up-regulation remains unclear.METHODWe analysed PTTG1 differential expression in PC-3, DU-145 and LNCaP tumor cell lines, cultured in the presence of the methyl-transferase inhibitor 5-Aza-2'-deoxycytidine. We also tested whether the CpG island mapping PTTG1 proximal promoter evidenced a differential methylation pattern in differentiated thyroid cancer biopsies concordant to their PTTG1 immunohistochemistry status. Finally, we performed whole-genome LOH studies using Affymetix 50 K microarray technology and FRET analysis to search for allelic imbalances comprising the PTTG1 locus.CONCLUSIONOur data suggest that neither methylation alterations nor LOH are involved in PTTG1 over-expression. These data, together with those previously reported, point towards a post-transcriptional level of misregulation associated to PTTG1 over-expression. PB BioMed Central Ltd YR 2008 FD 2008-04-21 LK http://hdl.handle.net/10668/1762 UL http://hdl.handle.net/10668/1762 LA en NO Hidalgo M, Galan JJ, Sáez C, Ferrero E, Castilla C, Ramirez-Lorca R, et al. Methylation alterations are not a major cause of PTTG1 misregulation. BMC Cancer. 2008; 8:110 NO Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; DS RISalud RD Apr 11, 2025