Effects of interferon-alpha on cell cycle regulatory proteins in leukemic cells.
One prominent activity of Interferons (IFNs) is their ability to induce cell cycle arrest, and this effect has furthermore been proposed to be of major importance in mediating the clinical antitumor activity of IFNs. In several IFN sensitive established cell lines, a rapid upregulation of the cyclin dependent kinase inhibitor p21 occurs following IFN-alpha treatment, and is thought to play a major role as an effector for this phenomenon by triggering further events. The aim of this study was to investigate how these previous findings in established cells lines correlate with clinical material. We therefore, analyzed how IFN-alpha influences the cell cycle distribution, by analysis of cellular DNA content, and the level of various cell cycle regulatory proteins by Western blot analysis, in primary leukemic cells. In 5 of 10 examined acute myeloid leukemia samples and in 1 of 6 chronic lymphocytic leukemia sample a clear increase in p21 protein levels was detected following treatment with IFN-alpha, while p21 protein levels were unaffected by IFN treatment in any of the examined acute lymphoblastic leukemia samples. In our total material consisting of 21 patient samples all other cell cycle regulatory proteins studied (p27, Cyclin E, Cdk2), were largely unaffected by IFN treatment. These results confirm that IFN-alpha can act as a potent regulator of Cdk-inhibitor expression, and that the induction of p21 seems to be a primary event in IFN-alpha mediated cell cycle regulation.
Szeps
Michael
M
Department of Oncology-Pathology, Karolinska Hospital and Institute, 171 76 Stockholm, Sweden.
Erickson
Sven
S
Gruber
Astrid
A
Castro
Juan
J
Einhorn
Stefan
S
Grandér
Dan
D
D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000187:drug effects* / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000187:drug effects / Q000378:metabolism; D004273:DNA, Neoplasm / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004273:DNA, Neoplasm; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins