CD30-mediated cell cycle arrest associated with induced expression of p21(CIP1/WAF1) in the anaplastic large cell lymphoma cell line Karpas 299

One of the major characteristics of anaplastic large cell lymphomas (ALCL) is the expression of the Ki-1/CD30 antigen. While the receptor mediates NF- kappaB-activation in Hodgkin's lymphomas, some data suggest the CD30-mediat ed apoptosis of other CD30-expressing cells. We were able to demonstrate th at activation of CD30 leads to different effects regarding cell proliferati on of the ALCL-derived cell lines Karpas 299 and JB6, Western and Northern blotting analysis re, revealed that CD30-induced growth inhibition of Karpa s 299 cells correlated with a strong upregulation of the cell cycle inhibit or p21(CIP1/WAF1). We found a non activating point mutation at codon 273 in exon 8 of the p53 gene in Karpas 299 cells which indicates an p53-independ ent mechanism for induced p21 expression. Abundant p21 protein expression r esulted in hypophosphorylation of the retinoblastoma protein (Rb) and inhib ition of the proliferating cell nuclear antigen (PCNA). CD30-stimulated cel ls showed no indications of apoptotic cell death, like genomic DNA fragment ation or cleavage of the caspase3 target protein poly (ADP-ribose) polymera se (PARP), Our results indicate that CD30 is able to mediate an p21-associa ted cell cycle arrest in ALCL with possible implications for prognosis and clinical treatment.