Functional activity and tumor-specific expression of dual oxidase 2 in pancreatic cancer cells and human malignancies characterized with a novel monoclonal antibody.
Functional activity and tumor-specific expression of dual oxidase 2 in pancreatic cancer cells and human malignancies characterized with a novel monoclonal antibody.
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DOI：
10.3892/ijo.2013.1821
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发表时间：
2013-04
影响因子：
5.2
通讯作者：
Roy K
中科院分区：
文献类型：
--
作者：
Wu Y;Antony S;Hewitt SM;Jiang G;Yang SX;Meitzler JL;Juhasz A;Lu J;Liu H;Doroshow JH;Roy K
双氧化酶 2 (Duox2) 是 NADPH 氧化酶基因家族的七个成员之一，在产生 H2O2 用于甲状腺激素生物合成方面发挥着关键作用，并且是呼吸道上皮和胃肠道宿主防御系统的组成部分。最近的证据表明，Duox2 表达的调节受到促炎细胞因子的控制，并且 Duox2 诱导的活性氧 (ROS) 会导致炎症相关的组织损伤，这种损伤发生在两种癌前炎症性疾病中：慢性胰腺炎和炎症性肠病。由于没有可靠的 Duox 抗体市售，我们报告了针对 Duox2 的鼠单克隆抗体 (MAb)（克隆 Duox S-12）的开发，及其用于表征人类肿瘤、肿瘤细胞系和正常组织中 Duox2 表达的用途。 Duox S-12 通过免疫印迹、免疫荧光显微镜和免疫组织化学（其中存在膜和细胞质染色）特异性检测内源和异位表达的 Duox2 蛋白。 Duox S-12 检测到的 Duox2 表达在功能上与表达 Duox2 及其同源成熟因子 DuoxA2 的胰腺癌细胞中 H2O2 的产生相关。虽然 Duox S-12 由于 Duox1 和 Duox2 之间广泛的氨基酸同源性而识别异位表达的 Duox1 蛋白，但人类肿瘤（甲状腺癌除外）中缺乏大量 Duox1 mRNA 表达，使我们能够通过免疫组织化学评估多种正常和恶性组织中的 Duox2 表达。 Duox2 在许多人类癌症中表达水平升高，尤其是前列腺癌、肺癌、结肠癌和乳腺癌，而脑肿瘤和淋巴瘤的表达频率最低。这里描述的 Duox 特异性单克隆抗体为进一步检查 Duox 依赖性活性氧产生在炎症相关癌发生中的作用提供了一种有前景的工具，其中氧化剂色调的改变在细胞生长和增殖中发挥着关键作用。
Dual oxidase 2 (Duox2), one of the seven members of the NADPH oxidase gene family, plays a critical role in generating H2O2 for thyroid hormone biosynthesis and as an integral part of the host defense system of the respiratory epithelium and the gastrointestinal tract. Recent evidence suggests that the regulation of Duox2 expression is under the control of pro-inflammatory cytokines and that Duox2-induced reactive oxygen species (ROS) contribute to the inflammation-related tissue injury that occurs in two pre-malignant, inflammatory conditions: chronic pancreatitis and inflammatory bowel disease. Because no reliable Duox antibodies are commercially available, we report the development of a murine monoclonal antibody (MAb) to Duox2 (clone Duox S-12) and its use for the characterization of Duox2 expression in human tumors, tumor cell lines and normal tissues. Duox S-12 specifically detected both endogenously- and ectopically-expressed Duox2 protein by immunoblotting, immunofluorescence microscopy and immunohistochemistry (where both membranous and cytoplasmic staining were present). Duox2 expression detected by Duox S-12 was functionally coupled to the generation of H2O2 in pancreatic cancer cells that expressed Duox2 and its cognate maturation factor DuoxA2. Although Duox S-12 recognizes ectopically expressed Duox1 protein because of the extensive amino acid homology between Duox1 and Duox2, the lack of substantial Duox1 mRNA expression in human tumors (except thyroid cancer) allowed us to evaluate Duox2 expression across a wide range of normal and malignant tissues by immunohistochemistry. Duox2 was expressed at elevated levels in many human cancers, most notably tumors of the prostate, lung, colon and breast while brain tumors and lymphomas demonstrated the lowest frequency of expression. The Duox-specific monoclonal antibody described here provides a promising tool for the further examination of the role of Duox-dependent reactive oxygen production in inflammation-related carcinogenesis, where alterations in oxidant tone play a critical role in cell growth and proliferation.
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影响因子：
4.8
作者：
Grasberger, Helmut;Refetoff, Samuel
通讯作者：
Refetoff, Samuel
影响因子：
4
作者：
Lipinski, Simone;Till, Andreas;Rosenstiel, Philip
通讯作者：
Rosenstiel, Philip
影响因子：
4.3
作者：
ORR, FW;ADAMSON, IYR;YOUNG, L
通讯作者：
YOUNG, L
NADPH 氧化酶同源物和辅助基因在人类癌细胞系、肿瘤和邻近正常组织中的表达。
影响因子：
3.3
作者：
Juhasz A;Ge Y;Markel S;Chiu A;Matsumoto L;van Balgooy J;Roy K;Doroshow JH
通讯作者：
Doroshow JH
影响因子：
50.3
作者：
Guerra C;Collado M;Navas C;Schuhmacher AJ;Hernández-Porras I;Cañamero M;Rodriguez-Justo M;Serrano M;Barbacid M
通讯作者：
Barbacid M