BIOLOGIC AND THERAPEUTIC SIGNIFICANCE OF MYB EXPRESSION IN HUMAN-MELANOMA

We investigated the therapeutic potential of employing antisense oligo deoxynucleotides to target the disruption of MYB, a gene which has bee n postulated to play a pathogenetic role in cutaneous melanoma. We fou nd that MYB was expressed at low levels in several human melanoma cell lines. Also, growth of representative lines in vitro was inhibited in a dose- and sequence-dependent manner by targeting the MYB gene with unmodified or phosphorothioate-modified antisense oligodeoxynucleotide s. Inhibition of cell growth correlated with specific decrease of MYB mRNA. In SCID mice bearing human melanoma tumors, infusion of MYB anti sense transiently suppressed MYB gene expression but effected longterm growth suppression of transplanted tumor cells. Toxicity of the oligo deoxynucleotides was minimal in mice, even when targeted to the murine Myb gene. These results suggest that the MYB gene may play an importa nt, though undefined, role in the growth of at least some human melano mas. Inhibition of MYB expression might be of use in the treatment of this disease.