Immortalization of human small airway epithelial cells by ectopic expression of telomerase
Immortalization of human small airway epithelial cells by ectopic expression of telomerase
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DOI：
10.1093/carcin/bgi016
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发表时间：
2005-04-01
期刊：
影响因子：
4.7
通讯作者：
Hei, TK
中科院分区：
文献类型：
--
作者：
Piao, CQ;Liu, L;Hei, TK
通过异位表达人端粒酶逆转录酶（hTERT）建立了两株永生化人气道上皮细胞系。这些细胞系已连续培养> 200个群体倍增（PD）。其特征在于hTERTmRNA的过表达、延长的端粒长度和较高的端粒酶活性。这些细胞的早期传代（< 20 PD）表达的p16蛋白水平与其亲本细胞相当。在后期传代（> 150 PD）中，p16蛋白降低，但在用甲基化抑制剂5-Aza-CdR处理后恢复到早期传代水平。染色体分析表明，近二倍体核型，虽然与增益或某些染色体的损失和一些稳定的易位在两个细胞系。在这些细胞系中未发现p53基因改变。它们在生长中保持锚定依赖性，并且在裸鼠中无致瘤性。这两种细胞系是首次报道的通过hTERT表达而不掺入病毒或其他基因的永生化人气道上皮细胞系，其可作为研究支气管癌发生的有用模型系统。
Two immortalized human airway epithelial cell lines were established by the ectopic expression of human telomerase reverse transcriptase (hTERT). These cell lines have been continuously cultured for > 200 population doublings (PDs). They are characterized by an overexpression of hTERT mRNA, elongated telomere length and higher telomerase activity. Early passage of these cells (< 20 PDs) expressed the p16 protein at a level comparable to their parental cells. In later passages (> 150 PDs), p16 protein was decreased but recovered to the early passage level upon treatment with a methylation inhibitor, 5-Aza-CdR. Chromosome analysis showed a near-diploid karyotype albeit with a gain or loss of certain chromosomes and a few stable translocations in both cell lines. No p53 gene alterations were found in these cell lines. They remained anchorage dependent in growth and were non-tumorigenic in nude mice. These two cell lines are the first reported immortalized human airway epithelial cell lines by hTERT expression without incorporation of virus or other genes, which may serve as a useful model system for studies on bronchial carcinogenesis.