This is supported by several lines of evidence including the (i) upregulation of SPRY4 by the rival oncogene only in cell lines exhibiting suppression and in none of the nonsuppressed lines, (ii) stronger growth inhibitory effects of SPRY4 in the antagonistic compared to neutral lines, (iii) direct tumor suppression in vivo by SPRY4 and (iv) partial rescue from oncogene antagonism with depletion of SPRY4. SPRYs and SPREDs comprise a family of proteins which are engaged in a negative regulatory loop in that both are activated by, and serve to repress, MAPK signaling [13]. This evidence concerns the gene SPRY4 and neoplasm.