Identification of a genetic signature of activated signal transducer and activator of transcription 3 in human tumors
Identification of a genetic signature of activated signal transducer and activator of transcription 3 in human tumors
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DOI：
10.1158/0008-5472.can-04-4281
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发表时间：
2005-06-15
期刊：
影响因子：
11.2
通讯作者：
Frank, DA
中科院分区：
文献类型：
--
作者：
Alvarez, JV;Febbo, PG;Frank, DA
信号转导和转录激活因子 3 (STAT3) 是一种转录因子，在多种人类肿瘤中被激活，可能在恶性转化中发挥直接作用。然而，STAT3 调节促进肿瘤发生的完整靶基因尚不清楚。我们创建了一个在小鼠成纤维细胞中表达 STAT3 STAT3-C 组成型活性形式的系统，并用它来识别 STAT3 靶标。我们发现这些靶标的一部分，包括调节细胞生长、存活和分化的转录因子，在一系列人类肿瘤中共表达。使用组织微阵列的免疫组织化学染色，我们发现这些靶标在含有激活的 STAT3 的乳腺和前列腺肿瘤中富集。最后，我们证明 STAT3 是这些基因在乳腺癌细胞系中表达所必需的。总而言之，这些结果确定了一组 STAT3 靶标，这些靶标可能介导其在肿瘤发生中的作用。
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated in diverse human tumors and may play a direct role in malignant transformation. However, the full complement of target genes that STAT3 regulates to promote oncogenesis is not known. We created a system to express a constitutively active form of STAT3, STAT3-C, in mouse fibroblasts and used it to identify STAT3 targets. We showed that a subset of these targets, which include transcription factors regulating cell growth, survival, and differentiation, are coexpressed in a range of human tumors. Using immunohistochemical staining of tissue micro-arrays, we showed that these targets are enriched in breast and prostate tumors harboring activated STAT3. Finally, we showed that STAT3 is required for the expression of these genes in a breast cancer cell line. Taken together, these results identify a cohort of STAT3 targets that may mediate its role in oncogenesis.