The prevalence of interferon-alpha transcription defects in malignant melanoma.
The type I interferons, interferon-alpha (IFN-alpha) and interferon-beta (IFN-beta), are situated on the short arm of chromosome 9, specifically 9p21-22. This locus lies very close to an area that is deleted or rearranged in nearly half of all melanomas tested. The identification of 9p rearrangements in both melanoma precursor lesions (dysplastic naevi) and primary lesions has implicated the 9p locus in the early stages of melanoma development. Recent evidence has demonstrated that metastatic melanoma cell lines have a specific loss of IFN-alpha gene expression, a defect that appears to occur at the level of transcription. In this study, we examined the expression of IFN-alpha in cell lines isolated from the various stages of melanoma progression, with a view to determine the prevalence of the IFN-alpha transcription defects exhibited by malignant melanoma, and to assess whether the loss of IFN-alpha expression was particular to a certain stage of melanoma progression. We showed that all the melanoma cell lines tested (n=20) demonstrated an inability to express IFN-alpha, a defect that was reflected in the apparent inactivity of the IFN-alpha promoter. These defects were found to occur in cells isolated from early melanomas, lending support to the hypothesis that IFN-alpha has a role in the aetiology of malignant melanoma.
Price
Karen L
KL
RAFT Institute of Plastic Surgery, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN, UK.
Herlyn
Meenhard
M
Dent
Carolyn L
CL
Gewert
Dirk R
DR
Linge
Claire
C
D000970:Antineoplastic Agents / Q000378:metabolism; D045744:Cell Line, Tumor; D002899:Chromosomes, Human, Pair 9; D004268:DNA-Binding Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics* / Q000378:metabolism; D008544:Melanocytes; D008545:Melanoma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D029082:Sendai virus; D012878:Skin Neoplasms / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D012333:RNA, Messenger; D012334:RNA, Neoplasm