Abstract
IFN-alpha has presented antitumor effect in about 50% of carcinoid tumor patients, though the antitumor mechanism of IFN-alpha is still to be elucidated. In this study we demonstrated that IFN-alpha could result in accumulation of S-phase population and upregulation of cyclin-dependent kinase inhibitor (CKI), p27. Moreover, IFN-alpha inhibits DNA synthesis assessed by [3H] thymidine incorporation and colony formation on soft agar. Immunodepletion of p27 increased CDK2- and cyclin E-associated kinase activities. These data suggest that IFN-alpha exerts its antiproliferative effects in the neuroendocrine differentiated cell lines by: 1) inhibition of DNA synthesis and colony formation, 2) upregulation on the mRNA and protein expressions of the CKI, p27.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2',5'-Oligoadenylate Synthetase / genetics
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2',5'-Oligoadenylate Synthetase / metabolism
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CDC2-CDC28 Kinases*
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Carcinoid Tumor / drug therapy*
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Carcinoid Tumor / enzymology*
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Carcinoid Tumor / pathology
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Carcinoid Tumor / secondary
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Cell Cycle / drug effects
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Cell Cycle Proteins*
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Cell Division / drug effects
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Colonic Neoplasms / pathology
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Cyclin E / antagonists & inhibitors*
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclin-Dependent Kinases / antagonists & inhibitors*
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DNA / biosynthesis
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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GTP-Binding Proteins*
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Humans
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Interferon Regulatory Factor-1
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Interferon Type I / pharmacology*
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Interferon Type I / therapeutic use
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Lymphatic Metastasis
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Microtubule-Associated Proteins / antagonists & inhibitors
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Microtubule-Associated Proteins / biosynthesis*
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Myxovirus Resistance Proteins
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Pancreatic Neoplasms / pathology
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Proteins / genetics
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Proteins / metabolism
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Proto-Oncogene Proteins*
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RNA, Messenger / biosynthesis
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Recombinant Proteins
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Thymidine / metabolism
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Tumor Cells, Cultured
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Tumor Stem Cell Assay
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Tumor Suppressor Proteins*
Substances
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Cell Cycle Proteins
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Cyclin E
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DNA-Binding Proteins
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IRF1 protein, human
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Interferon Regulatory Factor-1
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Interferon Type I
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Microtubule-Associated Proteins
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Myxovirus Resistance Proteins
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Phosphoproteins
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Proteins
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Proto-Oncogene Proteins
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RNA, Messenger
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Recombinant Proteins
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Tumor Suppressor Proteins
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Cyclin-Dependent Kinase Inhibitor p27
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DNA
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Protein Serine-Threonine Kinases
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CDC2-CDC28 Kinases
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CDK2 protein, human
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CDK4 protein, human
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinases
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2',5'-Oligoadenylate Synthetase
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GTP-Binding Proteins
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Thymidine