The c-myc oncogene: use of a biological prognostic marker as a potential target for gene therapy in melanoma.
The c-myc oncogene has been shown to be overexpressed in a number of malignancies, and may play an important role in the pathogenesis of malignant melanoma. Previous prognostic studies have demonstrated c-myc overexpression in a range of cutaneous melanomas, and levels of c-myc oncoprotein expression have been shown to correlate with clinical outcome in both primary and secondary disease. The purpose of this study was to investigate the in vitro manipulation of c-myc expression using antisense oligonucleotides. The human melanoma cell lines A375M, Be11 and WM115 were treated with c-myc antisense oligonucleotides, and the cellular growth was compared with controls. Antisense oligonucleotides reduced the growth rate of all three cell lines, and produced a reduction in c-myc gene expression as measured by flow cytometry. The growth inhibitions in the A375M, Be11 and WM115 cell lines at 72 h were 36.6%, 35.8% and 29.3%, respectively. Each of these was significantly different from control cultures (P<0.01). The c-myc antisense produced a mean 75% reduction in c-myc oncoprotein expression when compared with controls in the A375M cells (P<0.001), a 49% reduction in the Be11 cells (P<0.001) and a 28% reduction in the WM115 cells (P=0.005). This study demonstrates the importance of the c-myc oncogene in controlling melanoma growth. It suggests that blocking the expression of this gene, using an antisense approach, reduces melanoma cell growth, and may potentially provide a novel gene-therapy strategy for the treatment of advanced melanoma.
Chana
J S
JS
RAFT Institute of Plastic Surgery, Mount Vernon Hospital, Northwood, Middlesex, UK.
Grover
R
R
Tulley
P
P
Lohrer
H
H
Sanders
R
R
Grobbelaar
A O
AO
Wilson
G D
GD
D002455:Cell Division; D005434:Flow Cytometry / Q000379:methods; D016259:Genes, myc; D005819:Genetic Markers; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D009363:Neoplasm Proteins / Q000378:metabolism; D016376:Oligonucleotides, Antisense; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D014407:Tumor Cells, Cultured
D005819:Genetic Markers; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc