原癌基因c-fos在人乳腺癌耐药株MCF-7/ADR中的表达及意义

Expression and significance of the proto-oncogene c-fos in human breast cancer multidrug resistant MCF-7/ADR cells

目的探讨原癌基因c-fos在人乳腺癌细胞MCF-7/ADR多药耐药形成中的作用。方法采用MTT法测定化疗药物阿霉素(adriamycin,ADR)、紫杉醇、依托泊甙对人乳腺癌敏感株MCF-7和耐药株MCF-7/ADR的IC_(50);用real time PCR法检测MCF-7/ADR和MCF-7的c-fos mRNA表达差异;用逆转录PCR(RT-PCR)和Western blot法检测ADR对MCF-7中c-fos mRNA和蛋白表达的诱导作用。结果相对于MCF,MCF-7/ADR对ADR、紫杉醇、依托泊甙的耐药倍数分别为39.94,102.34和12.16;MCF-7/ADR中c-fos mRNA表达明显高于MCF-7;ADR可诱导MCF-7中c-fos mRNA和蛋白呈时间依赖性表达。结论 c-fos在MCF-7/ADR多药耐药中起重要作用,有可能成为耐药肿瘤诊断和治疗的新分子靶点。

Objective To explore the effect of the proto-oncogene c-fos on multidrug resistance（MDR）of human breast cancer MCF-7/ ADR cells.Methods MTT assay was used to elucidate IC_（50）values of adriamycin（ADR）,paclitaxel and etoposide against breast cancer cells.The expression of c-fos mRNA in MCF-7 and MCF-7/ADR cells was determined using real time PCR.The induction of cfos mRNA and protein by ADR in MCF-7 cells was examined by reverse transcriptase-PCR and Western blot,respectively.Results Compared with MCF-7,the resistance fold of ADR,paclitaxel and etoposide against MCF-7/ADR was 39.94,102.34 and 12.16,respectively. The level of c-fos mRNA in MCF-7/ADR was significantly higher than that in MCF-7 cells（P0.01）.The expression of c-fos mRNA and protein was induced by ADR in a time-dependent manner in MCF-7.Conclusion The results suggest that the proto-oncogene c-fos may play an important role in MDR of MCF-7/ADR cells,and it would be a novel molecular target for the diagnosis and treatment of breast cancer.