Pro-oncogene Pokemon promotes breast cancer progression by upregulating survivin expression.
Pro-oncogene Pokemon promotes breast cancer progression by upregulating survivin expression.
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原癌基因 Pokemon 通过上调生存素表达促进乳腺癌进展
DOI：
10.1186/bcr2843
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发表时间：
2011-03-10
期刊：
影响因子：
--
通讯作者：
Jiang Y
中科院分区：
文献类型：
--
作者：
Zu X;Ma J;Liu H;Liu F;Tan C;Yu L;Wang J;Xie Z;Cao D;Jiang Y
简介：Pokemon是一种致癌转录因子，参与细胞生长、分化和肿瘤发生，但对其在人类乳腺癌中的作用知之甚少。在这项研究中，我们的目的是揭示口袋妖怪在乳腺癌的进展和患者的生存的作用，并了解其潜在的mechanism.Methods：组织芯片分析乳腺癌组织的患者完整的临床病理数据和超过20年的随访被用来评估口袋妖怪的表达及其与疾病的进展和预后的相关性。使用过表达Pokemon的MCF-7细胞的DNA微阵列分析来鉴定Pokemon靶基因。结果：182例乳腺癌组织中有158例（86.8%）存在Pokemon的过表达，其表达与肿瘤大小（P = 0.0148）和淋巴结转移（P = 0.0014）相关。Pokemon表达导致总体（n = 175，P = 0.01）和疾病相关（n = 79，P = 0.0134）患者生存率更差。DNA微阵列分析显示，在MCF-7乳腺癌细胞中，Pokemon调节了至少121个基因的表达，这些基因参与了几种信号传导和代谢途径，包括抗凋亡生存素。在临床标本中，Pokemon与Survivin的表达高度相关（n = 49，r = 0.6799，P < 0.0001）。ChIP和定点突变表明，口袋妖怪诱导生存素表达的GT盒结合在其promoter.Conclusions：口袋妖怪促进乳腺癌的进展，通过上调生存素的表达，因此可能是一个潜在的目标，为治疗这种恶性肿瘤。
Introduction:Pokemon is an oncogenic transcription factor involved in cell growth, differentiation and oncogenesis, but little is known about its role in human breast cancer. In this study, we aimed to reveal the role of Pokemon in breast cancer progression and patient survival and to understand its underlying mechanisms.Methods:Tissue microarray analysis of breast cancer tissues from patients with complete clinicopathological data and more than 20 years of follow-up were used to evaluate Pokemon expression and its correlation with the progression and prognosis of the disease. DNA microarray analysis of MCF-7 cells that overexpress Pokemon was used to identify Pokemon target genes. Chromatin immunoprecipitation (ChIP) and site-directed mutagenesis were utilized to determine how Pokemon regulates survivin expression, a target gene.Results:Pokemon was found to be overexpressed in 158 (86.8%) of 182 breast cancer tissues, and its expression was correlated with tumor size (P = 0.0148) and lymph node metastasis (P = 0.0014). Pokemon expression led to worse overall (n = 175, P = 0.01) and disease-related (n = 79, P = 0.0134) patient survival. DNA microarray analyses revealed that in MCF-7 breast cancer cells, Pokemon regulates the expression of at least 121 genes involved in several signaling and metabolic pathways, including anti-apoptotic survivin. In clinical specimens, Pokemon and survivin expression were highly correlated (n = 49, r = 0.6799, P < 0.0001). ChIP and site-directed mutagenesis indicated that Pokemon induces survivin expression by binding to the GT boxes in its promoter.Conclusions:Pokemon promotes breast cancer progression by upregulating survivin expression and thus may be a potential target for the treatment of this malignancy.
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影响因子：
8.8
作者：
Grabowski, P;Kühnel, T;Mühr-Wilkenshoff, F;Heine, B;Stein, H;Höpfner, M;Germer, CT;Scherübl, H
通讯作者：
Scherübl, H
影响因子：
6.2
作者：
Giltnane, Jennifer M.;Moeder, Christopher B.;Rimm, David L.
通讯作者：
Rimm, David L.
影响因子：
8
作者：
Islam, A;Kageyama, H;Nakagawara, A
通讯作者：
Nakagawara, A
影响因子：
4.1
作者：
Li, FZ;Altieri, DC
通讯作者：
Altieri, DC
影响因子：
4.8
作者：
Lee, DK;Suh, D;Hur, MW
通讯作者：
Hur, MW