Differential expression of the p27Kip1 mRNA in IFN-sensitive and resistant cell lines.
IFNs arrest the growth of a small cell lung cancer (SCLC) cell line NCI-H82 in the G1 phase but not the growth of the derived cell line NCI-H82R. Progression through the G1 phase is controlled by positive and negative regulatory genes. Oncoviral genes can override this control. In this study, we compared the effects of human IFN alpha 2b on the mRNA levels of the Cdk inhibitor p27Kip1 in NCI-H82, NCI-H82R and HPV 16 E7-transfected NCI-H82 cell lines. Induction of the 2-5 Oligoadenylate synthetase (2-5 OAS) gene was used as a marker of IFN-dependent signal transduction The expression of p27Kip1 mRNA increased at 48 and 72 hr after IFN alpha 2b addition in sensitive cells. In contrast, p27Kip1 mRNA had only slight variations in both the resistant and E7-transfected cells. Interestingly, the E7-transfected NCI-H82 cells became resistant to the IFN alpha 2b anti-proliferative effect. Our results suggest that p27Kip1 could be a key mediator of the IFN alpha 2b-induced growth arrest and that HPV 16 E7 might affect p27Kip1 inducibility, originating IFN alpha 2b-resistant cells.
Moro
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A
División de Farmacéuticos, Centro de Ingeniería Genética y Biotecnología (CIGB), Ciudad de La Habana, Cuba. farma@ingen.cigb.edu.cu
Calixto
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A
Suárez
E
E
Araña
M J
MJ
Perea
S E
SE
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D050760:Cyclin-Dependent Kinase Inhibitor p27; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008858:Microscopy, Phase-Contrast; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics*; D009856:Oncogene Proteins, Viral / Q000494:pharmacology; D027383:Papillomaviridae; D012333:RNA, Messenger / Q000378:metabolism*; D011994:Recombinant Proteins; D015398:Signal Transduction; D014162:Transfection; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; C085208:E7 protein, Human papillomavirus 6b; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008869:Microtubule-Associated Proteins; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015088:2',5'-Oligoadenylate Synthetase