STAT5 isoforms regulate colorectal cancer cell apoptosis via reduction of mitochondrial membrane potential and generation of reactive oxygen species
STAT5 isoforms regulate colorectal cancer cell apoptosis via reduction of mitochondrial membrane potential and generation of reactive oxygen species
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STAT5亚型通过降低线粒体膜电位和产生活性氧来调节结直肠癌细胞凋亡
DOI：
10.1002/jcp.22977
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发表时间：
2012-06-01
影响因子：
5.6
通讯作者：
Fang, Jing-Yuan
中科院分区：
文献类型：
--
作者：
Du, Wan;Wang, Ying-Chao;Fang, Jing-Yuan
尽管信号转导子和转录激活子5（STAT 5）蛋白的两种亚型STAT 5a和STAT 5 b具有94%的序列同一性，但它们由不同的基因编码。以前的研究一直无法清楚地定义STAT 5基因在结直肠癌（CRC）中的作用。为了研究STAT 5亚型在CRC肿瘤发生中的作用，进行免疫组织化学染色。STAT 5a/5 b在大肠腺癌组织中的表达明显高于正常大肠黏膜组织（P < 0.05），且大肠腺癌组织中STAT 5 b的表达明显高于STAT 5a（P < 0.05）。STAT 5 b的表达与TNM分期密切相关。为了描述STAT 5a/5 b在CRC癌变中的作用，我们研究了通过用小干扰RNA处理细胞而耗尽每种亚型的CRC细胞。STAT 5a和STAT 5 b均参与大肠癌细胞的生长、细胞周期进程和凋亡，并通过调控STAT基因下游靶点发挥作用。STAT 5 b对结直肠癌细胞凋亡的影响明显大于STAT 5a（P < 0.05），其作用是降低线粒体膜电位，产生活性氧。结论：STAT 5的两种亚型均参与了大肠癌细胞的生长和细胞周期进程，STAT 5 b在大肠癌的临床病理特征和大肠癌细胞凋亡中可能发挥比STAT 5a更重要的作用。J.细胞。227：2421-2429，2012。© 2011 Wiley Periodicals，Inc.
Although the two isoforms of signal transducer and activator of transcription 5 (STAT5) protein, STAT5a and STAT5b, have 94% sequence identity, they are encoded by different genes. Previous studies have been unable to define clearly the roles of the STAT5 genes in colorectal cancer (CRC). To investigate the role of STAT5 isoforms in CRC oncogenesis, immunohistochemical staining was performed. Colorectal adenocarcinomas showed higher expression of STAT5a/5b than normal colonic mucosa (P < 0.05), and STAT5b expression was significantly higher than that of STAT5a in colorectal adenocarcinoma tissue (P < 0.05). Furthermore, STAT5b expression was significantly associated with TNM stage. To delineate the roles of STAT5a/5b in CRC carcinogenesis, we studied CRC cells depleted of each isoform by treating the cells with small interfering RNA. Both STAT5a and STAT5b were found to be involved in cell growth, cell cycle progression, and apoptosis of CRC cells, and exerted their effects via the regulation of downstream targets of the STAT genes. However, STAT5b influenced CRC cell apoptosis more than STAT5a (P < 0.05), reducing mitochondrial membrane potential and generating reactive oxygen species. In conclusion, both isoforms of STAT5 are involved in the growth and cell cycle progression of CRC cells, STAT5b could play a more important role than STAT5a in the clinicopathological characteristics of CRC and CRC cell apoptosis. J. Cell. Physiol. 227: 2421–2429, 2012. © 2011 Wiley Periodicals, Inc.