4.8 Article

Identification of a genetic signature of activated signal transducer and activator of transcription 3 in human tumors

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CANCER RESEARCH
卷 65, 期 12, 页码 5054-5062

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AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-04-4281

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  1. NCI NIH HHS [CA79547] Funding Source: Medline

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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.

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