Biologic and therapeutic significance of MYB expression in human melanoma.
We investigated the therapeutic potential of employing antisense oligodeoxynucleotides to target the disruption of MYB, a gene which has been postulated to play a pathogenetic role in cutaneous melanoma. We found 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 oligodeoxynucleotides. Inhibition of cell growth correlated with specific decrease of MYB mRNA. In SCID mice bearing human melanoma tumors, infusion of MYB antisense transiently suppressed MYB gene expression but effected long-term growth suppression of transplanted tumor cells. Toxicity of the oligodeoxynucleotides was minimal in mice, even when targeted to the murine Myb gene. These results suggest that the MYB gene may play an important, though undefined, role in the growth of at least some human melanomas. Inhibition of MYB expression might be of use in the treatment of this disease.
Hijiya
N
N
Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia.
Zhang
J
J
Ratajczak
M Z
MZ
Kant
J A
JA
DeRiel
K
K
Herlyn
M
M
Zon
G
G
Gewirtz
A M
AM
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006400:Hematocrit; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009838:Oligodeoxyribonucleotides / Q000633:toxicity; D016376:Oligonucleotides, Antisense / Q000032:analysis / Q000627:therapeutic use* / Q000633:toxicity; D009857:Oncogenes / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense