金属镉应答新基因TEF-1δ的致癌力鉴定

Carcinogenicity identification of the novel cadmium-responsive gene TEF-1δ

目的 前期研究已发现金属镉应答新基因TEF -1δ转染NIH3T3细胞可致其编码蛋白质表达升高而引起细胞转化。本研究的目的是对TEF 1δ基因转化NIH3T3细胞的致癌能力和致瘤性进行鉴定。方法 软琼脂集落形成试验和裸鼠成瘤实验。结果 所有 4株不同的TEF 1δ转染发生转化的NIH3T3细胞在软琼脂培养中均显示锚非依赖性生长能力 ,形成明显的细胞集落。而非转化对照细胞在软琼脂上则无生长能力。转化细胞和对照细胞分别给裸鼠皮下注射 (每组 4只 ,5组共 2 0只 ) ,1周后 ,转化细胞组的绝大部分裸鼠下背部皮下开始出现肿瘤 ,4周后所有 4种不同转化细胞株接种的裸鼠全部长出大小不等的肿瘤 ,但非转化对照细胞于第 5周后仍无一只裸鼠出现肿瘤。提示TEF 1δ转基因转化细胞属恶性转化细胞 ,具有明显的致癌能力和致瘤作用。结论 根据本研究结果及前期发现 ,可以认为新发现的TEF

Objective The previous studies have shown that transfection of NIH3T3 cells with a novel cadmium related gene TEF-1δ resulted in overexpression of its encoded protein and then cell transformation. The objective of this study was to confirm the oncogenic and tumorigenic potential of the transformed NIH3T3 cells transfection mediated with TEF 1δ. Methods Soft agar assay and nude mouse tumorigenicity assay were used. Results All of the 4 different transformed NIH3T3 cell lines showed their capacities to grow as anchorage independent colonies on soft agar as compared with non transformed cells which had no colonies appeared. Similarly, tumors were found in almost all nude mice injected with the transformed cells 1 week(7 days) later and in all nude mice 4 weeks(28 days) later, but none of the mice injected with non transformed cells showed tumors even after 5 weeks (35 days) of inoculation. Conclusion Theses results indicated that the transformed NIH3T3 cells transfection mediated with TEF 1δ was strong oncogenic and tumorigenic. Based on the present and previous results, it was suggested that TEF-1δ could be a novel cadmium-responsive proto-oncogen.