Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Cientificas, Universidad de Sevilla Sevilla, Spain.
Front Oncol. 2012 Sep 6;2:112. doi: 10.3389/fonc.2012.00112. eCollection 2012.
MAP17 is a small 17 kDa non-glycosylated membrane protein previously identified as being overexpressed in carcinomas. Breast tumor cells that overexpress MAP17 show an increased tumoral phenotype with enhanced proliferative capabilities both in the presence or the absence of contact inhibition, decreased apoptotic sensitivity, and increased migration. MAP17-expressing clones also grow better in nude mice. The increased malignant cell behavior induced by MAP17 is associated with an increase in reactive oxygen species (ROS) production, and the treatment of MAP17-expressing cells with antioxidants results in a reduction in the tumorigenic properties of these cells. The MAP17-dependent increase in ROS and tumorigenesis relies on its PDZ-binding domain because disruption of this sequence by point mutations abolishes the ability of MAP17 to enhance ROS production and tumorigenesis. MAP17 is overexpressed in a great variety of human carcinomas, including breast tumors. Immunohistochemical analysis of MAP17 during cancer progression demonstrates that overexpression of the protein strongly correlates with tumoral progression. Generalized MAP17 overexpression in human carcinomas indicates that MAP17 can be a good marker for tumorigenesis and, especially, for malignant progression.
MAP17 是一种小的 17 kDa 非糖基化膜蛋白，先前被鉴定为在癌组织中过度表达。过度表达 MAP17 的乳腺癌细胞表现出增强的肿瘤表型，在有或没有接触抑制的情况下，增殖能力增强，凋亡敏感性降低，迁移能力增强。表达 MAP17 的克隆在裸鼠中也生长得更好。MAP17 诱导的恶性细胞行为增加与活性氧（ROS）产生增加有关，用抗氧化剂处理表达 MAP17 的细胞会降低这些细胞的致瘤特性。MAP17 依赖性 ROS 增加和肿瘤发生依赖于其 PDZ 结合域，因为点突变破坏该序列会使 MAP17 丧失增强 ROS 产生和肿瘤发生的能力。MAP17 在多种人类癌组织中过度表达，包括乳腺癌。在癌症进展过程中对 MAP17 的免疫组织化学分析表明，该蛋白的过度表达与肿瘤进展强烈相关。人类癌组织中 MAP17 的普遍过度表达表明 MAP17 可以作为肿瘤发生的良好标志物，特别是作为恶性进展的标志物。
