Proteome characterization of a human urothelial cell line resistant to the bladder carcinogen 4-aminobiphenyl.
Proteome characterization of a human urothelial cell line resistant to the bladder carcinogen 4-aminobiphenyl.
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DOI：
10.1186/1477-5956-5-6
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发表时间：
2007-05-03
期刊：
影响因子：
2
通讯作者：
Matullo G
中科院分区：
文献类型：
--
作者：
Pastorelli R;Saletta F;Carpi D;Campagna R;dell'Osta C;Schiarea S;Vineis P;Airoldi L;Matullo G
芳香胺4-氨基联苯（4-ABP）是一种已知的环境和职业污染物，是人类膀胱癌的主要病因。4-ABP代谢物能够形成DNA加合物，可能诱导突变并引发膀胱癌。接触4-ABP的细胞可能会对这种致癌物产生耐药性。本研究的目的是检测和鉴定膀胱癌RT112亚系对4-ABP获得性耐药中表达改变的蛋白，以阐明其机制。细胞裂解物的差异蛋白质组学分析显示，在4- abp耐药的人尿路上皮克隆中，细胞代谢和能量通路整体受到干扰，膜转运蛋白如膜联蛋白2过度表达。耐药克隆改变了许多与细胞凋亡减少直接或间接相关的蛋白（如层粘连蛋白A/C、程序性细胞死亡6相互作用蛋白）的表达，表明对4-ABP的耐药可能与细胞凋亡活性低有关。我们的数据提供了证据，证明细胞凋亡和膜转运蛋白的解除管制可能与抗癌细胞的选择密切相关。其中一些蛋白质可能有潜力作为耐药性和癌症风险的生物标志物。
The aromatic amine 4-aminobiphenyl (4-ABP) is an environmental and occupational contaminant known to be a major etiological agent of human bladder cancer. 4-ABP metabolites are able to form DNA adducts that may induce mutations and initiate bladder carcinogenesis. Cells exposed to 4-ABP may develop resistance to the carcinogen. The aim of the present study was to detect and identify proteins whose expression is altered in the bladder carcinoma RT112 sub-lines selected for acquired resistance to 4-ABP, in order to disentangle the mechanisms. Differential proteome analysis of cell lysates showed an overall perturbation in cell metabolism and energy pathways in the 4-ABP-resistant human urothelial clones, with over-expression of membrane trafficking proteins such as annexin 2. The resistant clones had altered expression of many proteins linked directly (i.e. lamin A/C, programmed cell death 6 interacting protein) or indirectly (i.e. 94 kDa glucose-regulated protein, fatty acid-binding protein) to decreased apoptosis, suggesting that resistance to 4-ABP might be associated with low apoptotic activity. Our data provide evidence that deregulation of apoptosis and membrane trafficking proteins might be strongly implicated in the selection of carcinogen resistant cells. Some of these proteins might have potential as biomarkers of resistance and cancer risk.
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