ISOLATION OF A NOVEL SRY-RELATED GENE THAT IS EXPRESSED IN HIGH-METASTATIC K-1735 MURINE MELANOMA-CELLS

To identify genes differentially expressed in association with metasta tic potential of K-1735 mouse melanoma cells, the mRNA differential di splay method was applied to compare mRNAs from high- and low-metastati c K-1735 cells. A novel gene was identified as being expressed in high -metastatic cells but not in low-metastatic cells. Sequence analysis r evealed that this gene had an open reading frame of 538 amino acid res idues containing a Sry high-mobility group (HMG) box domain, known as a DNA binding motif, particularly in the Sox family genes. This gene s howed the highest homology to the human SOX9 gene, which is the respon sible gene for an inherited disease, campomelic dysplasia. Thus, this gene was designated the Sox21 gene (the 21st Sor family gene). The Sox 21 gene was mapped to mouse Chromosome 15, to which neither genes cont aining the HMG bog region nor the loci of hereditary diseases similar to campomelic dysplasia have been previously mapped. This gene was hig hly conserved and specifically expressed in the brain. These results s uggest that expression of the Sox21 gene is involved in the developmen t of nerve systems and may function to enhance the metastatic potentia l of K-1735 mouse melanoma cells of nerve cell origin. (C) 1997 Academ ic Press