Interferon system defects in human malignant melanoma.
We have examined the ability of melanoma cell lines and normal human melanocytes, which have demonstrable intact IFN genes, to secrete both IFN-alpha and IFN-beta in response to induction with virus. Normal melanocytes were found to secrete both IFN-alpha and IFN-beta after virus induction. In contrast, although all but one of the melanoma lines tested were capable of secreting IFN-beta, none were capable of IFN-alpha secretion. This phenomenon was not due to defects in either translation of IFN-alpha mRNA or secretion of IFN-alpha proteins, since transfection of melanoma lines with a constitutive IFN-alpha 2b expression vector resulted in the secretion of high levels of IFN. On further examination, this inability to express natural IFN-alpha appeared to be due to a defect in activation of the IFN-alpha promoters, since constructs containing the IFN-alpha promotor were completely unresponsive to viral infection in melanoma cells but inducible in melanocytes. These results show that there is a specific disruption of IFN-alpha gene activation rather than IFN-beta in melanoma lines and suggest that this is due to disruption of a trans-acting IFN-alpha gene transcription factor. Disruption of this factor and its consequences may be important in the development of malignant melanoma.
Linge
C
C
Biology Division, Wellcome Foundation Ltd., Beckenham, Kent, United Kingdom.
Gewert
D
D
Rossmann
C
C
Bishop
J A
JA
Crowe
J S
JS
D001483:Base Sequence; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D016147:Genes, Tumor Suppressor; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics*; D016899:Interferon-beta / Q000235:genetics*; D008545:Melanoma / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014407:Tumor Cells, Cultured
D002087:Butyrates; D016898:Interferon-alpha; D020148:Butyric Acid; D016899:Interferon-beta