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-mediated apoptosis of other CD30-expressing cells. We were able to demonstrate that activation of CD30 leads to different effects regarding cell proliferation of the ALCL-derived cell lines Karpas 299 and JB6. Western and Northern blotting analysis revealed that CD30-induced growth inhibition of Karpas 299 cells correlated with a strong upregulation of the cell cycle inhibitor 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-independent mechanism for induced p21 expression. Abundant p21 protein expression resulted in hypophosphorylation of the retinoblastoma protein (Rb) and inhibition of the proliferating cell nuclear antigen (PCNA). CD30-stimulated cells showed no indications of apoptotic cell death, like genomic DNA fragmentation or cleavage of the caspase-3 target protein poly (ADP-ribose) polymerase (PARP). Our results indicate that CD30 is able to mediate an p21-associated cell cycle arrest in ALCL with possible implications for prognosis and clinical treatment.
Hübinger
G
G
Department of Internal Medicine III, University of Ulm, Robert-Koch-Str. 8, D-89081 Ulm, Germany.
Müller
E
E
Scheffrahn
I
I
Schneider
C
C
Hildt
E
E
Singer
B B
BB
Sigg
I
I
Graf
J
J
Bergmann
L
L
D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis; D001483:Base Sequence; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D017730:Ki-1 Antigen / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology; D015854:Up-Regulation
D000906:Antibodies; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017730:Ki-1 Antigen; D018809:Proliferating Cell Nuclear Antigen; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53