人支气管上皮细胞恶性转化中凋亡敏感性及bcl-2的变化

目的: 揭示细胞凋亡敏感性在人癌细胞体外恶性转化动态过程中的变化。方法:用已获部分恶性的SV₄₀T转染的人支气管上皮细胞系M为材料, 通过凋亡TDT原位标记、染色体FISH、RNA及蛋白检测等技术,研究同一株细胞恶性转化过程中凋亡及bcl-2、P53基因的变化。结果:恶性转化的M后代细胞较未转化的M前代细胞对顺铂诱发细胞凋亡现象不敏感;bcl-2基因的转录和表达在M后代细胞明显高于M前代细胞,而且在M细胞恶性转化进程中呈积累现象;P53蛋白在M前、后代细胞均表达。结论:bcl-2过表达使细胞对凋亡敏感性下降在人支气管上皮细胞恶性转化中起重要作用;P53蛋白的灭活不是此SV₄₀T转染细胞恶性转化进程中bcl-2表达积累的主要原因。

Alteration of apoptotic susceptibility and bcl-2 gene in malignant transformation of human bronchial epithelial cells

AIM: To demonstrate the susceptibility of cell apoptosis varies during the progress of cell malig- nant transformation from human being in vitro. METHODS: A SV40T - transfected human bronchial epithelial im- mortalized cell line (called M) was selected in this work, which has acquired some characteristics of malignant trans- formation at the later passage. The alterations of apoptosis and bcl- 2, P53 genes between early and later passage of M cells were investigated by means of TDT labeling in situ, chromosome FISH, RNA and protein testing, etc. RE- SULTS: Incidence of apoptosis induced by cis - platin was significantly lower in later than in early passages of M. Levels of bcl - 2 mRNA and protein in later passages were higher than early passages of M, and overxpression of bcl -2 was accumulated following the development of cellular malignancy. P53 protein level was as high in early as in later passages. CONCLUSION: Overexpression of bcl - 2 decreases the cellular sensitivity to apoptotic inductors plays an important role during progress of carcinogenesis in human bronchial epithelial cancers. The inactivation of P53 protein in the SV40 - T transfected M cell line may be one of reasons of bcl - 2 overexpression, but not associated with the accumulation of bcl - 2 expressed level during cell transformation.