Expression of anion exchanger 1 sequestrates p16 in the cytoplasm in gastric and colonic adenocarcinoma
Expression of anion exchanger 1 sequestrates p16 in the cytoplasm in gastric and colonic adenocarcinoma
复制标题
阴离子交换剂 1 的表达将 p16 隔离在胃和结肠腺癌的细胞质中。
DOI：
10.1593/neo.07403
复制
发表时间：
2007-10-01
期刊：
影响因子：
4.8
通讯作者：
Fu, Guo-Hui
中科院分区：
文献类型：
--
作者：
Shen, Wei-Wei;Wu, Jun;Fu, Guo-Hui
P16(Ink4a)(P16)与细胞周期蛋白依赖性激酶4/6结合，负向调节细胞生长。最近的研究已经使人们对p16的其他生物学功能有了更多的了解；然而，涉及的详细机制仍然不清楚。在这篇文章中，我们展示了阴离子交换器1(AE1)在中低分化胃和结肠腺癌细胞中的意外表达，以及它与p16的相互作用，从而将该蛋白隔离在细胞质中。未检测到p16和ae1基因改变。在这些细胞中强制表达AE1使更多的p16滞留在细胞质中，而小干扰RNA介导的细胞内AE1的沉默诱导p16从细胞质释放到细胞核，导致细胞死亡和肿瘤细胞的生长抑制。通过对胃癌和结肠癌组织标本的分析，我们发现83.33%的胃癌和56.52%的结肠癌在胞浆中共表达AE1和p16。我们得出结论：AE1在胃腺癌和结肠腺癌的发病机制中起重要作用，p16功能障碍是一条新的致癌途径。
p16(INK4A) (p16) binds to cyclin-dependent kinase 4/6 and negatively regulates cell growth. Recent studies have led to an understanding of additional biologic functions for p16; however, the detailed mechanisms involved are still elusive. In this article, we show an unexpected expression of anion exchanger 1 (AE1) in the cytoplasm in poorly and moderately differentiated gastric and colonic adenocarcinoma cells and in its interaction with p16, thereby sequestrating the protein in the cytoplasm. Genetic alterations of p16 and AE1 were not detectable. Forced expression of AE1 in these cells sequestrated more p16 in the cytoplasm, whereas small interfering RNA-mediated silencing of AE1 in the cells induced the release of p16 from the cytoplasm to the nucleus, leading to cell death and growth inhibition of tumor cells. By analyzing tissue samples obtained from patients with gastric and colonic cancers, we found that 83.33% of gastric cancers and 56.52% of colonic cancers coexpressed AE1 and p16 in the cytoplasm. We conclude that AE1 plays a crucial role in the pathogenesis of gastric and colonic adenocarcinoma and that p16 dysfunction is a novel pathway of carcinogenesis.