CD30 Activation Causes Cell Cycle Arrest Of The CD30+ Anaplastic Large Cell Lymphoma Cell Lines

Year 2000, Volume: 1 Issue: 2, 29 - 32, 01.08.2000

Edi Levı Walther Pfeıfer Marshall E. Kadın

Abstract

Aims: CD30 activation causes growth inhibition of the systemic anaplastic large cell lymphoma cell lines. The mechanism of growth inhibition is not well characterized. Since CD30 does not have a death domain like the other tumor necrosis factor receptor superfamily members Fas and TNFRI, the mechanism of growth inhibition is a matter of controversy. Methods: In this study, we analyzed the growth inhibitory effects of CD30 activation on the systemic ALCL cell line Karpas 299 by using a CD30 activating antibody HeFi-1. We first investigated the presence of apoptosis by Annexin V and propidium iodide staining using flow cytometric analysis. We did not observe any apoptotic changes or cell death during the 72 hours following CD30 activation, despite a decrease in thymidine incorporation, which prompted us to investigate the possibility of cell cycle arrest caused by CD30 activation. Results: Upon synchronization of the cells and incubation with the HeFi-1 antibody, we observed a partial arrest at G1 phase demonstrated by propidium iodide staining of the permeabilized cells. We then investigated the expression of cell cycle inhibitory proteins p16, p21, p27 and retinoblastoma protein (Rb) by Western blotting. We observed expression of p21 and hypo-phosphorylation of Rb protein secondary to CD30 activation. Significance: These results are consistent with cell cycle arrest in the G1 phase of the cell cycle following CD30 activation. This finding is contrary to the accepted belief that CD30 activation causes apoptosis. These findings may help the development of new therapeutic strategies against nodal anaplastic large cell lymphomas.

Keywords

CD30, Anaplastic large cell lymphoma, Hodgkin’s disease, NF-kappaB, SN50, HeFi-1, cell cyclearrest

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