Lack of mda-6/WAF1/CIP1-mediated inhibition of cyclin-dependent kinases in interferon-alpha resistant murine B16 melanoma cells.
Previously we demonstrated that IFN-alpha augments mda-6/WAF1 and inhibits cyclin-dependent kinases in a p53-independent fashion in B 16 murine melanoma cells. On the other hand, IFN-gamma activates p53 expression without affecting the mda-6/WAF1 system. Combination of the two IFNs is additive. B16 cells acquire IFN-alpha resistant but IFN-gamma sensitive phenotype after long term IFN-alpha treatment (B16alpha cells). Here we demonstrate the absence of mda-6/WAF1-associated repression of cyclin-dependent kinases, but the existence of p53-dependent c-myc inhibition in IFN-gamma-treated B16alpha cells. Clearly, selective desensitization of IFN-alpha related growth regulation does not influence the IFN-gamma 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.
Arany
I
I
Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston 77555-1019, USA.
Fleischmann
C M
CM
Tyring
S K
SK
Fleischmann
W R
WR
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D004794:Enzyme Repression; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000201:enzymology*; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016898:Interferon-alpha; D009363:Neoplasm Proteins; D007371:Interferon-gamma; D018844:Cyclin-Dependent Kinases