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Methylation alterations are not a major cause of PTTG1 missregulation

BACKGROUND: On 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...

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Autores principales: Hidalgo, Manuel, Galan, Jose Jorge, Sáez, Carmen, Ferrero, Eduardo, Castilla, Carolina, Ramirez-Lorca, Reposo, Pelaez, Pablo, Ruiz, Agustin, Japón, Miguel A, Royo, Jose Luis
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377271/
https://www.ncbi.nlm.nih.gov/pubmed/18426563
http://dx.doi.org/10.1186/1471-2407-8-110
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author Hidalgo, Manuel
Galan, Jose Jorge
Sáez, Carmen
Ferrero, Eduardo
Castilla, Carolina
Ramirez-Lorca, Reposo
Pelaez, Pablo
Ruiz, Agustin
Japón, Miguel A
Royo, Jose Luis
author_facet Hidalgo, Manuel
Galan, Jose Jorge
Sáez, Carmen
Ferrero, Eduardo
Castilla, Carolina
Ramirez-Lorca, Reposo
Pelaez, Pablo
Ruiz, Agustin
Japón, Miguel A
Royo, Jose Luis
author_sort Hidalgo, Manuel
collection PubMed
description BACKGROUND: On 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. METHOD: We 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. CONCLUSION: Our 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 missregulation associated to PTTG1 over-expression.
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spelling pubmed-23772712008-05-13 Methylation alterations are not a major cause of PTTG1 missregulation Hidalgo, Manuel Galan, Jose Jorge Sáez, Carmen Ferrero, Eduardo Castilla, Carolina Ramirez-Lorca, Reposo Pelaez, Pablo Ruiz, Agustin Japón, Miguel A Royo, Jose Luis BMC Cancer Research Article BACKGROUND: On 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. METHOD: We 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. CONCLUSION: Our 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 missregulation associated to PTTG1 over-expression. BioMed Central 2008-04-21 /pmc/articles/PMC2377271/ /pubmed/18426563 http://dx.doi.org/10.1186/1471-2407-8-110 Text en Copyright © 2008 Hidalgo et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hidalgo, Manuel
Galan, Jose Jorge
Sáez, Carmen
Ferrero, Eduardo
Castilla, Carolina
Ramirez-Lorca, Reposo
Pelaez, Pablo
Ruiz, Agustin
Japón, Miguel A
Royo, Jose Luis
Methylation alterations are not a major cause of PTTG1 missregulation
title Methylation alterations are not a major cause of PTTG1 missregulation
title_full Methylation alterations are not a major cause of PTTG1 missregulation
title_fullStr Methylation alterations are not a major cause of PTTG1 missregulation
title_full_unstemmed Methylation alterations are not a major cause of PTTG1 missregulation
title_short Methylation alterations are not a major cause of PTTG1 missregulation
title_sort methylation alterations are not a major cause of pttg1 missregulation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377271/
https://www.ncbi.nlm.nih.gov/pubmed/18426563
http://dx.doi.org/10.1186/1471-2407-8-110
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