Interferon-gamma downregulates epidermal growth factor receptors on human melanoma cells.
Unregulated expression of epidermal growth factor receptor (EGF-R) is a common event in neoplastic transformation and has been shown to be associated with melanocytic tumor progression. Modulation of such a receptor by pharmacological agents could therefore be of clinical interest. We have studied EGF-R expression, its response to epidermal growth factor (EGF) and modulation effects by interferon gamma (IFN gamma) on human melanoma cells. Addition of EGF, anti-EGF and anti-EGF-R antibodies had no effect on proliferation of six melanoma cell lines tested. We report in this communication that EGF-R expression on human melanoma cells can be modulated by IFN-gamma. In the melanoma cell lines treated with IFN gamma, proliferative behavior was not affected; however, we demonstrate a downregulation of EGF-R expression on the protein level, by immunohistochemistry and flow cytometric analysis, and an accumulation of EGF-R mRNA by Northern blot analysis. The results suggest that IFN gamma downregulates EGF-R expression at a posttranscriptional level on human melanoma cells. This EGF/EGF-R interaction and its modulation by IFN gamma on human melanoma cells needs to be further clarified regarding its in vivo significance for the treatment and prognosis of malignant melanoma.
Worm
M
M
University Hospital Rudolf Virchow, Department of Dermatology, FU Berlin, Germany.
Makki
A
A
Dippel
E
E
Czarnetzki
B M
BM
Schadendorf
D
D
D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D007371:Interferon-gamma; D066246:ErbB Receptors