Biologic and therapeutic significance of MYB expression in human melanoma

Nobuko Hijiya, Jin Zhang, Mariusz Z. Ratajczak, Jeffrey A. Kant, Kim Deriel, Meenhard Herlyn, Gerald Zon, Alan M. Gewirtz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4499-4503
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number10
DOIs
StatePublished - May 10 1994

ASJC Scopus subject areas

  • General

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