Expression of dihydrodiol dehydrogenase plays important roles in apoptosis- and drug-resistance of A431 squamous cell carcinoma
Expression of dihydrodiol dehydrogenase plays important roles in apoptosis- and drug-resistance of A431 squamous cell carcinoma
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DOI：
10.1016/j.jdermsci.2005.11.007
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发表时间：
2006-03-01
影响因子：
4.6
通讯作者：
Wu, MT
中科院分区：
文献类型：
--
作者：
Chow, KC;Lu, MP;Wu, MT
背景：二氢二醇。脱氢酶（DDH）是醛酮还原酶超家族的成员之一，可能参与多环芳烃（PAH）等环境致突变物质的正常解毒过程。目的：探讨DDH在皮肤鳞状细胞癌（SCC）中的表达及其与肿瘤进展和预后的关系。用含有DDH靶向小干扰RNA（siRNA）的逆转录病毒载体转染A431细胞，进行RNA干扰（RNAi）。结果：DDH在鳞状细胞癌A431细胞中高表达，而在正常皮肤细胞、角质形成细胞、成纤维细胞、基底细胞癌细胞系中几乎不表达。结论：DDH可能通过诱导细胞凋亡和诱导耐药在SCC的发生发展中起重要作用。(c)2005年日本皮肤病研究学会。由Elsevier爱尔兰有限公司出版。保留所有权利。
Background: Dihydrodiol. dehydrogenase (DDH) is a member of the aldo-keto reductases superfamily which may be involved in normal detoxification process of environmental mutagenic hazards like polycyclic aromatic hydrocarbons (PAH). Previous clinical studies have demonstrated the over-expression of DDH in various types of cancers, including cutaneous squamous cell carcinoma (SCC), and its correlation with tumor progression and grave prognosis.Objective: To investigate possible mechanisms for DDH's correlation with tumor progression and unfavorable prognosis.Methods: DDH expression in SCC A431 cell line was examined by quantitative real-time PCR and immunoblotting. RNA interference (RNAi) by transduction with retro-virat vector containing DDH-targeting small interfering RNA was employed to inhibit DDH expression by A431 cells. With DDH expression inhibited or not, sensitivity of A431 cells to UVB-induced apoptosis and cytotoxicity of chemotherapeutic agent bleomycin were then examined and compared.Results: DDH was found highly expressed by SCC A431 cells, which was barely detectable in other normal or malignant cutaneous cells, including keratinocytes, fibroblast, and basal cell carcinoma cell tine. RNAi Inhibition of DDH expression in A431 cells led to increased sensitivity to UVB-induced apoptosis and cytotoxicity of bleomycin treatment.Conclusion: DDH may play important roles in tumor progression of SCC via induction of apoptosis- and drug-resistance. (c) 2005 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.