CD30-mediated cell cycle arrest associated with induced expression of p21CIP1/WAF1 in the anaplastic large cell lymphoma cell line Karpas 299
CD30-mediated cell cycle arrest associated with induced expression of p21CIP1/WAF1 in the anaplastic large cell lymphoma cell line Karpas 299
复制标题
DOI：
10.1038/sj.onc.1204128
复制
发表时间：
2001-02-01
期刊：
影响因子：
8
通讯作者：
Bergmann, L
中科院分区：
文献类型：
--
作者：
Hübinger, G;Müller, E;Bergmann, L
间变性大细胞淋巴瘤 (ALCL) 的主要特征之一是 Ki-1/CD30 抗原的表达。虽然该受体在霍奇金淋巴瘤中介导 NF-κB 激活，但一些数据表明 CD30 介导其他表达 CD30 的细胞凋亡。我们能够证明 CD30 的激活会对 ALCL 衍生细胞系 Karpas 299 和 JB6 的细胞增殖产生不同的影响，Western 和 Northern 印迹分析表明，CD30 诱导的 Karpas 299 细胞生长抑制与细胞周期抑制剂 p21(CIP1/WAF1) 的强烈上调相关。我们在 Karpas 299 细胞中的 p53 基因外显子 8 的密码子 273 处发现了一个非激活点突变，这表明诱导 p21 表达的 p53 独立机制。丰富的 p21 蛋白表达导致视网膜母细胞瘤蛋白 (Rb) 的低磷酸化和增殖细胞核抗原 (PCNA) 的抑制。 CD30 刺激的细胞没有显示出细胞凋亡的迹象，例如基因组 DNA 片段化或 caspase3 靶蛋白聚（ADP-核糖）聚合酶 (PARP) 的裂解。我们的结果表明 CD30 能够介导 ALCL 中 p21 相关的细胞周期停滞，可能对预后和临床治疗产生影响。
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 re, 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 caspase3 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.