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[Cancer Research 65, 5054-5062, June 15, 2005]
© 2005 American Association for Cancer Research

Molecular Biology, Pathobiology, and Genetics

Identification of a Genetic Signature of Activated Signal Transducer and Activator of Transcription 3 in Human Tumors

James V. Alvarez1,2, Phillip G. Febbo1,2, Sridhar Ramaswamy2,6, Massimo Loda1,3, Andrea Richardson3,4 and David A. Frank1,2,5

1 Department of Medical Oncology, Dana-Farber Cancer Institute, and Departments of 2 Medicine and 3 Pathology, Harvard Medical School; Departments of 4 Pathology and 5 Medicine, Brigham and Women's Hospital, Boston, Massachusetts; and 6 Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts

Requests for reprints: David A. Frank, Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Mayer 522B, Boston, MA 02115. Phone: 617-632-4714; Fax: 617-632-6356; E-mail: david_frank{at}dfci.harvard.edu.

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 microarrays, 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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