Effects of interferon alpha on the expression of p21cip1/waf1 and cellcycle distribution in carcinoid tumors.
2002 (English)In: Cancer Invest, Vol. 20, 348- p.Article in journal (Refereed) Published
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.
interferon alpha, gene expression, p21Cip1/Waf1, signal transduction, carcinoid, neuroendocrine tumor, cell cycle, cyclin dependent kinase
IdentifiersURN: urn:nbn:se:uu:diva-65540OAI: oai:DiVA.org:uu-65540DiVA: diva2:93451