Lack of mda-6/WAF1/CIP1-mediated inhibition of cyclin-dependent kinases in interferon-α resistant murine B16 melanoma cells

• Published in: Cancer letters Vol. 119; no. 2; pp. 237 - 240
• Main Authors: Aranya, Istvan, Fleischmann, Christina M., Tyring, Stephen K., Fleischmann, W.Robert
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 11.11.1997; Elsevier
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinases - metabolism; Cyclins - metabolism; Drug Resistance, Neoplasm; Enzyme Repression; Growth inhibition; Immunotherapy; Interferon-alpha - pharmacology; Interferon-gamma - pharmacology; Interferons; Medical sciences; Melanoma; Melanoma, Experimental - enzymology; Mice; Neoplasm Proteins - metabolism; Pharmacology. Drug treatments; Resistance; Tumor Cells, Cultured - drug effects; Resistance; Growth inhibition; Interferons; Melanoma; Alpha interferon; Cyclin; TP53 Gene; Immunotherapy; Cell cycle; Established cell line; Malignant melanoma; Negative therapeutic reaction; Tumor cell; Cytostase; Tumor suppressor gene; Enzyme; Transferases; Cytokine; Rodentia; Enzyme inhibitor; Malignant tumor; In vitro; Vertebrata; Mammalia; Treatment; Mouse; Kinase; Animal; Gamma interferon
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(97)00288-7

Previously we demonstrated that IFN-α augments mda-6/WAF1 and inhibits cyclin-dependent kinases in a p53-independent fashion in B16 murine melanoma cells. On the other hand, IFN-γ activates p53 expression without affecting the mda-6/WAF1 system. Combination of the two IFNs is additive. B16 cells acquire IFN-α resistant but IFN-γ sensitive phenotype after long term IFN-α treatment (B16α cells). Here we demonstrate the absence of mda-6/WAF1-associated repression of cyclindependent kinases, but the existence of p53-dependent c- myc inhibition in IFN-γ-treated B16α cells. Clearly, selective desensitization of IFN-α related growth regulation does not influence the IFN-γ associated pathway. Our results further support the coexistence of distinct growth regulatory mechanisms in B16 cells that can be activated by different IFN-types independently of each other.