Gene expression changes in human lung cells exposed to arsenic, chromium, nickel or vanadium indicate the first steps in cancer.
Gene expression changes in human lung cells exposed to arsenic, chromium, nickel or vanadium indicate the first steps in cancer.
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DOI：
10.1039/c2mt20074k
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发表时间：
2012-08
期刊：
影响因子：
--
通讯作者：
Costa M
中科院分区：
文献类型：
--
作者：
Clancy HA;Sun H;Passantino L;Kluz T;Muñoz A;Zavadil J;Costa M
致癌的复杂过程始于单个细胞的转化，以产生异常特征，例如接触抑制的丧失和不受控制的增殖——每种癌症都有这些特征。尽管癌症广泛流行，但引发癌症的早期事件仍然难以捉摸，如果不了解这些事件，癌症预防就很困难。在这里，我们发现接触砷、铬、镍或钒 (V) 会促进与异常生长相关的基因表达变化。我们将永生化的人支气管上皮细胞暴露于四种金属/类金属之一四到八周，并根据软琼脂中单细胞的贴壁独立生长来选择转化的克隆群体。我们检测到癌症相关基因表达的金属特异性足迹，该足迹在多个转化克隆中是一致的。这些基因表达变化在缺乏祖金属的情况下持续存在，导致多次细胞分裂。我们的结果表明，即使短暂接触致癌金属也可能会导致暴露细胞中基因表达的许多变化，并且从这些变化中，每种金属引起的引发癌症的特定变化可能会出现。
The complex process of carcinogenesis begins with transformation of a single cell to favor aberrant traits such as loss of contact inhibition and unregulated proliferation – features found in every cancer. Despite cancer’s widespread prevalence, the early events that initiate cancer remain elusive, and without knowledge of these events cancer prevention is difficult. Here we show that exposure to As, Cr, Ni, or Vanadium (V) promotes changes in gene expression that occur in conjunction with aberrant growth. We exposed immortalized human bronchial epithelial cells to one of four metals/metalloid for four to eight weeks and selected transformed clonal populations based upon anchorage independent growth of single cells in soft agar. We detected a metal-specific footprint of cancer-related gene expression that was consistent across multiple transformed clones. These gene expression changes persisted in the absence of the progenitor metal for numerous cell divisions. Our results show that even a brief exposure to a carcinogenic metal may cause many changes in gene expression in the exposed cells, and that from these many changes, the specific change(s) that each metal causes that initiate cancer likely arise.
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