The role of constitutively active signal transducer and activator of transcription 3 in ovarian turnorigenesis and prognosis
The role of constitutively active signal transducer and activator of transcription 3 in ovarian turnorigenesis and prognosis
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DOI：
10.1002/cncr.22293
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发表时间：
2006-12-01
期刊：
影响因子：
6.2
通讯作者：
Liu, Jinsong
中科院分区：
文献类型：
--
作者：
Rosen, Daniel G.;Mercado-Uribe, Imelda;Liu, Jinsong
背景信号转导子和转录激活子3（Signaltransducerandactivatoroftranscription 3，Stat 3）是一种潜在的转录因子，参与细胞凋亡和细胞周期进程的转录激活，是多种肿瘤性疾病的癌基因。然而，Stat 3在卵巢癌发生中的具体作用仍然知之甚少。本研究的目的是检测Stat 3激活对永生化的，非致瘤性卵巢上皮细胞系，并评估酪氨酸激活的Stat 3（pStat 3）的表达在303例卵巢癌的组织微阵列中，以确定其预后相关性，并将其表达与Stat 3的几个上游癌基因以及参与卵巢癌的癌基因相关联。凋亡和增殖。pStat 3的过表达是弱致瘤性的，并且在3个克隆中的1个中在小鼠中产生可测量的肿瘤。使用来自一大组原发性卵巢癌患者的组织微阵列，pStat 3的表达与生长因子受体（HER-2/neu和表皮生长因子受体[EGFR]）、白细胞介素6、增殖和凋亡标志物Ki-67、Bcl-2和Bcl-xL的表达相关，并与临床病理变量和患者生存率相关。肿瘤组织芯片中pStat 3的高表达与HER-2/neu、EGFR和Ki-67的高水平相关。未观察到总体pStat 3水平与所测试的任何其他临床病理变量之间的相关性。pStat 3的高核表达（> 10%的阳性染色细胞）与较差的总体存活率相关。pStat 3的激活和易位到细胞核是卵巢癌中的常见事件，与不良预后相关。Stat 3的激活机制、对下游靶点的影响及其在卵巢上皮细胞恶性转化中的作用尚需进一步研究。
BACKGROUND. Signal transducer and activator of transcription 3 (Stat3), which is a latent transcription factor that participates in the transcriptional activation of apoptosis and cell cycle progression, has been implicated as an oncogene in several neoplastic diseases. However, the specific role of Stat3 in ovarian carcinogenesis remains poorly understood. The objectives of the current study were to examine the effect of Stat3 activation on the phenotypic transformation of an immortalized, non-tumongenic ovarian epithelial cell line and to evaluate the expression of tyrosine-activated Stat3 (pStat3) in tissue microarrays from 303 ovarian carcinomas to determine its prognostic relevance and to correlate its expression with several upstream oncogenes of Stat3 and with the oncogenes involved in apoptosis and proliferation.METHODS. overexpression of pStat3 was weakly tumorigenic and produced measurable tumors in mice in I of 3 clones. Using tissue microarrays from a large group of patients with primary ovarian carcinoma, the expression of pStat3 was correlated with the expression of growth factor receptors (HER-2/neu and epidermal growth factor receptor [EGFR]), interleukin 6, and the proliferation and apoptosis markers Ki-67, Bcl-2, and Bcl-xL and with clinicopathologic variables and patient survival.RESULTS. High pStat3 expression in the tumor tissue microarray was associated with high levels of HER-2/neu, EGFR, and Ki-67. No correlation was observed between overall pStat3 levels and any other clinicopathologic variables tested. High nuclear expression of pStat3 (> 10% of positive-stained cells) was linked with poor overall survival.CONCLUSIONS. The activation and translocation of pStat3 to the nucleus are frequent events in ovarian carcinoma that are associated with a poor prognosis. Further studies are needed to elucidate the mechanism of activation of Stat3, its effects on downstream targets, and its role in the neoplastic transformation of epithelial ovarian cells.