Specific Activation of a STAT Family Member in Xiphophorus Melanoma Cells

Abstract

Melanoma formation in the teleost fish Xiphophorus is caused by the uncontrolled activity of the genetically defined tumor locus Tu. The critical component of this locus is the Xmrk oncogene encoding a subclass I receptor tyrosine kinase. Overexpression and constitutive activation of the Xmrk receptor triggers a set of specific signal transduction events eventually resulting in the malignant phenotype. We have identified a melanoma-specific DNA–protein complex which seems to depend on Xmrk activation as shown in a heterologous cell system. The critical component of this complex, which directs transcriptional activation in the melanoma cells, proved to be a fish homologue of STAT5. Two other STAT factors, STAT1 and STAT3, implied in signaling by the Xmrk-related EGF receptor, were not activated in this particular cell type. Thus, Xmrk initiates very specific signaling pathways and transcriptional responses in Xiphophorus melanoma.