TIF3镉应答基因的致癌性

Carcinogenicity Identification of a Novel Cadmium-Responsive Gene

[目的 ]前期研究发现 ,镉相关新基因TIF3 (基因文库添码 :AF2 710 72 )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TIF3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试验。 [结果 ]所有 4株不同的TIF3转染的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 ) ,4周后所有接种转化细胞的裸鼠全部长出大小不等的肿瘤 ,但非转化的对照细胞于第 5周后仍无 1只裸鼠出现肿瘤。提示TIF3转基因转化细胞属恶性转化细胞 ,具有一定的致癌能力和致瘤作用。 [结论 ]根据本研究结果及前期发现 。

The previous studies have shown that transfection of NIH3T3 cells with a novel cadmium related gene TIF3 (GenBank Accession Number AF271072) resulted in overexpression of its encoded protein inducing NIH3T3 cell transformation when transfected. The objective of this study is to confirm the oncogenic and tumorigenic potential of the transformed NIH3T3 cells transfection mediated with TIF3. Soft agar assay and nude mouse tumorigenicity assay were carried out. All of the 4 different transformed NIH3T3 cell lines showed their capacity to grow as anchorage independent colonies on soft agar as compared with non transformed cells that showed no colonies formed. Similarly,100% athymic nude mice inoculated with these transformed cells formed tumors within 4 weeks (28 days) of inoculation,but none of tumors in the mice injected with non transformed cells was found even 5 weeks (35 days) after inoculation. [Conclusion] These results indicate that the transformed NIH3T3 cells transfection mediated with TIF3 are strong oncogenic and tumorigenic. Based on the present and previous results,it might be concluded that TIF3 is a novel cadmium responsive proto oncogen.