Noteborn M H, Zhang Y H, van der Eb A J
Leadd, P.O. Box 9503, 2300 RA, Leiden, The Netherlands.
Mutat Res. 1998 May 25;400(1-2):447-55. doi: 10.1016/s0027-5107(98)00016-5.
Tumor formation is caused by an imbalance between cell replication and apoptosis, which is a physiological form of cell death. For instance, UV damage can result in tumor formation due to mutations of the tumor-suppressor gene p53, a major apoptosis-inducing protein. Over-expression of the proto-oncogene Bcl-2, due to chromosomal translocation, can also inhibit apoptosis resulting in, e.g., lymphomas and leukemias. Anti-tumor therapies are often based on induction of apoptosis mediated via p53 and/or inhibited by Bcl-2, which explains the frequently poor results of anti-tumor treatment. The avian-virus-derived protein 'Apoptin', induces apoptosis in a p53-independent way, is stimulated by Bcl-2 and is insensitive to BCR-ABL, another inhibitor of chemotherapeutic agents. Apoptin induces apoptosis in human transformed/tumorigenic cells but not in normal diploid cells. Co-synthesis of SV40 large T antigen and Apoptin results in induction of apoptosis, illustrating that the establishment of a stable transformed state is not required. UV-irradiation causes an aberrant SOS-response in primary diploid cells from cancer-prone individuals and renders such cells susceptible to Apoptin-induced apoptosis. All these features make Apoptin a potential candidate as a therapeutic and diagnostic tool in cancer treatment.
肿瘤形成是由细胞复制与凋亡之间的失衡引起的，凋亡是一种生理性细胞死亡形式。例如，紫外线损伤可因肿瘤抑制基因p53（一种主要的凋亡诱导蛋白）的突变而导致肿瘤形成。由于染色体易位，原癌基因Bcl-2的过度表达也可抑制凋亡，从而导致例如淋巴瘤和白血病。抗肿瘤治疗通常基于通过p53介导的凋亡诱导和/或被Bcl-2抑制，这解释了抗肿瘤治疗常常效果不佳的原因。源自禽病毒的蛋白“凋亡素”以不依赖p53的方式诱导凋亡，受Bcl-2刺激，且对另一种化疗药物抑制剂BCR-ABL不敏感。凋亡素可在人转化/致瘤细胞中诱导凋亡，但在正常二倍体细胞中则不会。SV40大T抗原与凋亡素的共合成导致凋亡诱导，这表明不需要建立稳定的转化状态。紫外线照射会在易患癌症个体的原代二倍体细胞中引发异常的SOS反应，并使这些细胞易受凋亡素诱导的凋亡影响。所有这些特性使凋亡素成为癌症治疗中一种潜在的治疗和诊断工具候选物。
