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Effects of interferon alpha on the expression of p21cip1/waf1 and cellcycle distribution in carcinoid tumors.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
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2002 (English)In: Cancer Invest, Vol. 20, 348- p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2002. Vol. 20, 348- p.
Keyword [en]
interferon alpha, gene expression, p21Cip1/Waf1, signal transduction, carcinoid, neuroendocrine tumor, cell cycle, cyclin dependent kinase
Identifiers
URN: urn:nbn:se:uu:diva-65540OAI: oai:DiVA.org:uu-65540DiVA: diva2:93451
Available from: 2008-06-15 Created: 2008-06-15 Last updated: 2011-01-13

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Zhou, YWang, SOberg, K

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