摘要
目的克隆α粒子辐射致细胞恶性转化相关基因。方法采用mRNA差异显示技术识别原代大鼠气管上皮细胞同α粒子辐射诱发恶性转化的大鼠气管上皮细胞之间的差别表达基因。结果共克隆到15个可能同α粒子辐射致细胞恶性转化相关的差异表达基因片段（ESRs），共向GenBank登录7条新基因序列。其中克隆ZG35同大鼠AnnednⅠ基因高度同源，AnnetinⅠ作为表皮生长因子受体激酶的底物被认为可能参与细胞增殖信号的转导;克隆ZC52同新型大鼠羧酸酯酶前体物基因高度同源;克隆ZG52同人SR蛋白激酶Ⅱ基因（SRPKZ）的3’端具有一定的同源性，SRPK2的功能为参与前-mRNA剪切的调控;克隆ZA73为新基因片段;克隆ZC66同肿瘤转移抑制基因nm23高度同源，序列分析提示nm23在恶性转化的细胞中存在突变。Northern杂交证实上述基因片段在恶转的大鼠气管上皮细胞中高表达。结论AnnexinⅠ、羧酸酯酶前体物基因、ZG52、nm23等可能参与α粒子辐射诱发大鼠气管上皮细胞恶性转化的过程。
Objective To isolate genes involved in neoplastic transformation induced by α-particales.Methods The differential display technique was ed to identify differentially expressed mRNA species between preimary and neoplastic transformed rat tracheal epithelial (RTE) cells induced by a particles. Results 15 differentially displayed gene fragments were cloned and sequenced Seven novel ESTs were submitted to GenBank.Homoloyg searching revealed that clone ZG35 was highly homologous to rat Annexin I gene which was thought to be involved in mitogenic signal transduction as a substrate of epidermal growth factor receptor/kinase. Clone ZC52 was nearly identical to a novel rattus norvegicus gene for carboxylesterase precursor, clone ZG52 was 3' similar to human SRPK2 gene suggesting it may be a novel SRPK2 related related involved in pre-mRNA splicing. Clone ZA73 was a novel gene fragments, and clone ZC66 was highly homologous to rat nucleoside diphesphate kinase gene or metastasis suppressor gene nm23, sequence analysis suggested that nm23 might be mutated in the transformed RTE cells. Northem hybridization confirmed the above gene or gene fragments to be up-regulated in the transformed RTE cells. Conclusion These results provide clues to elucidate the nechanisms of radiation oncogenesis and suggest that Annexin i, carboxylesterase precuresor gene, ZG52 and nm23 may be involved in the neoplastic transformation induced by α-particles radiation.
出处
《中华医学杂志》
CAS
CSCD
北大核心
1999年第10期754-756,共3页
National Medical Journal of China
基金
国家自然科学基金!39600033
中国人民解放军总后勤部重点招标课题
