Lack of p21waf1 and p27kip1 protein induction by interferon-alpha2a in human melanoma cell lines.
The ability of human recombinant interferon-alpha2a (IFNalpha2a) to induce the expression of cyclin-dependent kinase inhibitors p21waf1 and p27kip1 consequent to signal transducers and activators of transcription (STAT) protein activation was investigated in six human melanoma cell lines with different susceptibilities to the antiproliferative effect of the cytokine. All the cell lines expressed IFNalpha and IFNalpha/beta receptors. Exposure for 24 h to IFNalpha2a markedly enhanced the nuclear expression of STAT1 and STAT2 proteins in all the cell lines. However, no induction of p21waf1 or p27kip1 was consistently observed. Overall, results from the study suggest that the induction of such cyclin-dependent kinase inhibitors is not a major mechanism for the antiproliferative effect of IFNalpha2a, at least in human melanoma cell lines.
Bearzatto
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Divisione di Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
Orlandi
L
L
De Marco
C
C
Daidone
M G
MG
Zaffaroni
N
N
D015153:Blotting, Western; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000096:biosynthesis; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008869:Microtubule-Associated Proteins; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D053633:Receptor, Interferon alpha-beta