title: Methylation alterations are not a major cause of PTTG1 misregulation.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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 misregulation associated to PTTG1 over-expression.
authors.affiliation: Service of General Surgery-B, Hospital Universitario 12 de Octubre, Madrid, 28041, Spain. mhidalgo.hdoc@salud.madrid.org
authors.forename: Manuel
authors.initials: M
authors.lastname: Hidalgo
authors.forename: Jose Jorge
authors.initials: JJ
authors.lastname: Galan
authors.forename: Carmen
authors.initials: C
authors.lastname: Sáez
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ferrero
authors.forename: Carolina
authors.initials: C
authors.lastname: Castilla
authors.forename: Reposo
authors.initials: R
authors.lastname: Ramirez-Lorca
authors.forename: Pablo
authors.initials: P
authors.lastname: Pelaez
authors.forename: Agustin
authors.initials: A
authors.lastname: Ruiz
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Japón
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Royo
mesh_terms: D002277:Carcinoma / Q000378:metabolism; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005838:Genotype; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064249:Securin; D013964:Thyroid Neoplasms / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D009363:Neoplasm Proteins; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human