Cadmium down-regulates expression of XIAP at the post-transcriptional level in prostate cancer cells through an NF-κB-independent, proteasome-mediated mechanism
Cadmium down-regulates expression of XIAP at the post-transcriptional level in prostate cancer cells through an NF-κB-independent, proteasome-mediated mechanism
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DOI：
10.1186/1476-4598-9-183
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发表时间：
2010-07-09
期刊：
影响因子：
37.3
通讯作者：
Kolenko, Vladimir M.
中科院分区：
文献类型：
--
作者：
Golovine, Konstantin;Makhov, Peter;Kolenko, Vladimir M.
背景：镉已被列为人类致癌物，通过职业和环境暴露影响健康。镉的生物半衰期很长（>25年），这是因为它的排泄动力学是平坦的。前列腺是镉积累水平最高的器官之一。重要的是，前列腺癌患者似乎有较高水平的镉在循环和前列腺tissue.Results：在目前的报告中，我们首次证明，镉下调X-连锁的凋亡抑制蛋白（XIAP）在前列腺癌细胞的表达。镉介导的XIAP耗竭通过NF-κ B非依赖性蛋白酶体介导的机制发生在转录后水平，并且与前列腺癌细胞对TNF-α介导的凋亡的敏感性增加一致。长期镉治疗导致选择前列腺癌细胞的耐药表型。镉选择的PC-3 cells.Conclusions：镉耐药细胞的选择可能代表了一种适应性生存机制，可能有助于前列腺恶性肿瘤的进展。
Background: Cadmium has been classified as a human carcinogen, affecting health through occupational and environmental exposure. Cadmium has a long biological half-life (>25 years), due to the flat kinetics of its excretion. The prostate is one of the organs with highest levels of cadmium accumulation. Importantly, patients with prostate cancer appear to have higher levels of cadmium both in the circulation and in prostatic tissues.Results: In the current report, we demonstrate for the first time that cadmium down-regulates expression of the X-linked inhibitor of apoptosis protein (XIAP) in prostate cancer cells. Cadmium-mediated XIAP depletion occurs at the post-transcriptional level via an NF-kappa B-independent, proteasome-mediated mechanism and coincides with an increased sensitivity of prostate cancer cells to TNF-alpha-mediated apoptosis. Prolonged treatment with cadmium results in selection of prostate cancer cells with apoptosis-resistant phenotype. Development of apoptosis-resistance coincides with restoration of XIAP expression in cadmium-selected PC-3 cells.Conclusions: Selection of cadmium-resistant cells could represent an adaptive survival mechanism that may contribute to progression of prostatic malignancies.