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

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.