953. STAT5 Is Phosphorylated in Malignant Melanoma Leading to Proliferation Via Activation of ERK: Potential for Anti-Tumor Therapy

Altered signaling pathways are key regulators of cellular functions in tumor cells. We investigated several aspects of the JAK/STAT pathway in melanoma cell lines and patient samples and compared them with human primary melanocytes. Interestingly, the signal transducers and activators of transcription (STAT)5 and STAT3 were activated in clinical melanoma specimens and the endogenous suppressors of cytokine signaling (SOCS)-2 and SOCS3 were significantly reduced. In addition, bcl-x, bcl-2 and c-myc were frequently upregulated in melanoma specimens. A dominant negative STAT5B led to reduced cell growth and a reduction of activated extracellular-regulated kinases (ERK)-1/2 (p44/42 mitogen-activated protein kinase) which are critically involved in cell proliferation and apoptosis. Our study revealed strong activation of STAT5 and STAT3 signaling in clinical melanoma leading to cell growth via ERK1/2. This altered signaling pathway may serve as a molecular target in skin gene therapy.