Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007095 (carcinoid)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Inhibition of CDK2, CDK4 and cyclin E and increased expression of p27Kip1 during treatment with interferon-alpha in carcinoid tumor cells. 1070 44

Interferon alpha (IFN-alpha) has been shown to produce antitumor effects in 50-80% of carcinoid tumor patients and has demonstrated anti-proliferative effects in carcinoid tumor cells, but the mechanism is not well established. This study presents evidence that in a carcinoid tumor cell line, Bon1, IFN-alpha increases the expression of p21 and promotes nuclear translocation of endogenous p21. Furthermore, immunoprecipitation experiments demonstrated that p21 formed immuno-complexes with Stat1 and Stat2 in the nucleus of cells. Interferon alpha can decrease G1- and G2-phase cells, but increase S-phase population. The p21 mRNA expression is inversely correlated to the G1 population (r = -0.933, P < 0.05) and positively correlated to the S-phase population (r = 0.901, P < 0.05). In addition, IFN-alpha inhibited cyclin dependent kinases (CDK), CDK2-, CDK3-, CDK4-, and cyclin E- but not cyclin A-associated kinase activities. Immunodepletion of p21 resulted in a significant enhancement of CDK3 kinase activity (approximately 1.6-fold increase). These results suggest that the mechanism of antitumor and cell cycle regulation of IFN-alpha in carcinoid tumors may, at least in part, be p21-dependent. Based on these results, we conclude that IFN-alpha exerts antitumor effects by increased p21 expression in neuroendocrine tumors.
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PMID:Effects of interferon alpha on the expression of p21cip1/waf1 and cell cycle distribution in carcinoid tumors. 1202 30