Methylation alterations are not a major cause of PTTG1 misregulation.
Methylation alterations are not a major cause of PTTG1 misregulation.
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DOI：
10.1186/1471-2407-8-110
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发表时间：
2008-04-21
期刊：
影响因子：
3.8
通讯作者：
Royo JL
中科院分区：
文献类型：
--
作者：
Hidalgo M;Galan JJ;Sáez C;Ferrero E;Castilla C;Ramirez-Lorca R;Pelaez P;Ruiz A;Japón MA;Royo JL
在其生理细胞环境中，Pttg1控制着有丝分裂过程中姐妹染色单体的分离。在其与细胞阻止机制的串扰中，依赖于一个完整性检查点，因此获得了Securin的绰号。研究发现，Pttg1可促进3T3成纤维细胞的恶性转化，并在不同的肿瘤类型中过表达。最近，Pttg1还与不同的过程有关，如DNA修复，并被发现反式激活不同的细胞通路，包括c-myc、bax或p53等。Pttg1的过度表达与甲状腺、肺癌、结直肠癌患者的预后不良有关，不能排除这种影响也可能发生在其他类型的肿瘤中。尽管Pttg1的临床相关性和分子特征不断增加，但其上调的原因仍不清楚。我们分析了在甲基转移酶抑制剂5-氮杂-2‘-脱氧胞苷存在下培养的PC-3、DU-145和LNCaP肿瘤细胞系中Pttg1的差异表达。我们还测试了映射Pttg1近端启动子的CpG岛是否证明分化的甲状腺癌活检组织中存在与其Pttg1免疫组织化学状态一致的差异甲基化模式。最后，我们使用Affymetix 50K微阵列技术和FRET分析进行了全基因组杂合性缺失研究，以寻找包含Pttg1基因座的等位基因不平衡。我们的数据表明，Pttg1的过度表达既不涉及甲基化改变，也不涉及LOH。这些数据与以前报道的数据一起，表明了与Pttg1过度表达有关的转录后水平的错误调控。
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. 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. 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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Securin（HPTTG1）表达受人结肠直肠癌的β-catenin/tcf调节。
影响因子：
8.8
作者：
Hlubek, F;Pfeiffer, S;Budczies, J;Spaderna, S;Jung, A;Kirchner, T;Brabletz, T
通讯作者：
Brabletz, T
影响因子：
5.8
作者：
Hunter, JAC;Skelly, RH;Burrin, JM
通讯作者：
Burrin, JM
影响因子：
--
作者：
Zhang, X;Horwitz, GA;Melmed, S
通讯作者：
Melmed, S
影响因子：
4.8
作者：
Zhou, YL;Mehta, KR;Zhang, X
通讯作者：
Zhang, X
影响因子：
4.8
作者：
Castilla, Carolina;Congregado, Belen;Saez, Carmen
通讯作者：
Saez, Carmen