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Necdin, a Negative Growth Regulator, Is a Novel STAT3 Target Gene Down-Regulated in Human Cancer 1 2 2 1 3 4 Rachel Haviland , Steven Eschrich , Gregory Bloom , Yihong Ma , Susan Minton , Richard Jove *, W. Douglas Cress1* 1 Molecular Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America, 2 Biomedical Informatics, Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America, 3 Breast Cancer Program, Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America, 4 Beckman Research Institute, City of Hope National Medical Center, Duarte, California, United States of America Abstract Cytokine and growth factor signaling pathways involving STAT3 are frequently constitutively activated in many human primary tumors, and are known for the transcriptional role they play in controlling cell growth and cell cycle progression. However, the extent of STAT3’s reach on transcriptional control of the genome as a whole remains an important question. We predicted that this persistent STAT3 signaling affects a wide variety of cellular functions, many of which still remain to be characterized. We took a broad approach to identify novel STAT3 regulated genes by examining changes in the genome- wide gene expression profile by microarray, using cells expressing constitutively-activated STAT3. Using computational analysis, we were able to define the gene expression profiles of cells containing activated STAT3 and identify candidate target genes with a wide range of biological functions. Among these genes we identified Necdin, a negative growth regulator, as a novel STAT3 target gene, whose expression is down-regula