人类肺癌细胞系多抗药性肺癌细胞系中转运基因的过度表达
S P Cole1, G Bhardwaj, J H Gerlach
1Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada.
概括
耐化疗的肺癌细胞过度表达了一种新型的ATP结合磁带载体. 16号染色体上的基因放大与这种过度表达和耐药性相关,提供了新的治疗点.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 癌症研究 癌症研究
背景情况:
- doxorubicin 选择的 H69AR 肺癌细胞对多种化疗剂表现出耐药性.
- 这种耐药性并非由P-glycoprotein介导,P-glycoprotein是一种常见的多药耐药性载体.
- 了解新的抵抗机制对于开发有效的肺癌疗法至关重要.
研究的目的:
- 识别和描述新的基因和机制,使肺癌具有多药性耐药性.
- 研究H69AR细胞系中药物耐药性的遗传基础.
主要方法:
- 在H69AR细胞中分离对应于过度表达的信使RNA (mRNA) 的互补DNA (cDNA) 克隆.
- 使用杂交技术分析mRNA表达水平.
- 通过染色体映射 (染色体16,带p13.1) 进行基因放大分析.
- 基因放大和mRNA表达与药物敏感性的相关性.
主要成果:
- 发现一种新型mRNA (7.88.2千基) 在H69AR细胞中表达过多100到200倍,与父母的H69细胞相比.
- 这种过度表达与16号染色体上同系基因在带p13.1.1.的放大有关.
- 回归药物敏感性与减少mRNA表达和失去基因放大相关.
- 鉴定到的mRNA编码了ATP结合盒 (ABC) 超膜载体超家族中的一个成员.
结论:
- 一种新型的ATP结合磁带载体,由于染色体16上的基因放大而过度表达,有助于肺癌的多药性耐药性.
- 这一发现为克服肺癌中化疗耐药性提供了一个新的分子标.
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