Guangdong Provincial Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University, Lishui Road, Shenzhen 518055, People's Republic of China.
Breast Cancer Res. 2011 Mar 10;13(2):R26. doi: 10.1186/bcr2843.
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.
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.
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.
Pokemon promotes breast cancer progression by upregulating survivin expression and thus may be a potential target for the treatment of this malignancy.
Pokemon 是一种致癌转录因子，参与细胞生长、分化和致癌，但对其在人类乳腺癌中的作用知之甚少。本研究旨在揭示 Pokemon 在乳腺癌进展和患者生存中的作用，并了解其潜在机制。
使用具有完整临床病理数据和 20 多年随访的患者乳腺癌组织的组织微阵列分析来评估 Pokemon 的表达及其与疾病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。染色质免疫沉淀（ChIP）和定点突变用于确定 Pokemon 如何调节靶基因 survivin 的表达。
在 182 例乳腺癌组织中发现 158 例（86.8%） Pokemon 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 的表达导致总体（n = 175，P = 0.01）和疾病相关（n = 79，P = 0.0134）患者生存恶化。DNA 微阵列分析显示，在 MCF-7 乳腺癌细胞中，Pokemon 调节至少 121 个参与几种信号和代谢途径的基因的表达，包括抗凋亡的 survivin。在临床标本中，Pokemon 和 survivin 的表达高度相关（n = 49，r = 0.6799，P < 0.0001）。ChIP 和定点突变表明，Pokemon 通过结合其启动子中的 GT 盒诱导 survivin 的表达。
Pokemon 通过上调 survivin 的表达促进乳腺癌的进展，因此可能是治疗这种恶性肿瘤的潜在靶点。
