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目的:探讨c-myc肿瘤基因在乳腺癌早期发生过程中的活动状态.方法:利用1株人乳腺上皮细胞MCF-10F,经3种化学致癌物:benzo(a)yrene(BP),dimehthylbenz(a)anthracene(DMBA)和N-methyl-N-nitrosoguanidine(MN-NG)处理并建立了肿瘤性转化克隆细胞系.其中BP,BP1,BP1-E来自BP,DMBA,D3,D3-1来自DMBA,MNNG,M4来自MNNG处理的细胞,Southern核酸杂交.结果:c-myc基因的扩增出现在BP,D3和MNNG.Northern杂交显示c-mycmRNA在所有被处理的细胞株呈过度表达.同位素35S标记c-Myc蛋白与单克隆抗体免疫沉淀电泳分析发现67kuc-Myc蛋白除D3-1外的所有其它克隆株呈不同程度的过度表达.结论:c-mycmRNA的过度表达表明c-myc基因主要是通过增强其转录活性参与癌转化活动.c-mycmRNA的表达状态比c-myc的扩增更能说明它在细胞癌变中的作用.c-mycmRNA和c-Myc蛋白的过度表达是趋癌转化细胞和早期乳腺癌有价值的生物指标.
Objective: To investigate the activity of c-myc tumor gene in the early stage of breast cancer. METHODS: One human breast epithelial cell line MCF-10F was used and three chemical carcinogens were benzo(a)yrene(BP), dimehthylbenz(a) anthracene(DMBA) and N-methyl-N-nitrosoguanidine(MN-NG). Processing and establishment of a neoplastic transformed clonal cell line. Among them, BP, BP1, BP1-E were from BP, DMBA, D3, D3-1 were from DMBA, MNNG, and M4 were from MNNG-treated cells, and Southern nucleic acid hybridization. Results: The amplification of c-myc gene appeared in BP, D3 and MNNG. Northern hybridization showed that c-myc mRNA was overexpressed in all treated cell lines. Isotope 35S-labeled c-Myc protein and monoclonal antibody immunoprecipitation electrophoresis analysis found that 67kuc-Myc protein except D3-1 all showed different degrees of overexpression. Conclusion: The overexpression of c-myc mRNA indicates that c-myc gene is involved in cancer transformation activity mainly by enhancing its transcriptional activity. The expression of c-myc mRNA is more indicative of its role in cell carcinogenesis than the amplification of c-myc. The overexpression of c-myc mRNA and c-Myc protein is a valuable biomarker for cancer-transforming cells and early breast cancer.