Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila, Mexico.
Department of Gynecologic Oncology, Mexican Institute of Social Security, Torreon, Coahuila, México.
J Appl Toxicol. 2017 Oct;37(10):1195-1202. doi: 10.1002/jat.3481. Epub 2017 May 19.
The Hippo pathway regulates cell proliferation and apoptosis and it has been noted that loss of critical components of this pathway can lead to uncontrolled cell growth. Yes-associated protein (YAP) is an important component of this Hippo pathway because YAP is the nuclear effector of the Hippo tumor suppressor pathway and it is crucial for the response to oxidative stress induced by cellular process and by different xenobiotics, including arsenic. It has been proposed that YAP dysregulation can contribute to a malignant cellular phenotype acting as both a tumor suppressor and an oncogene. The aim of the study was to assess and compare the expression of YAP in neoplastic and non-neoplastic breast tissue of women chronically exposed to arsenic through drinking water. YAP expression was assessed by immunohistochemistry in 120 breast biopsies from women with breast cancer and from women with other non-neoplastic breast pathologies. Arsenic concentration was quantified in urine. The results disclosed a significant lower percentage of cytoplasm YAP expression in cases and that YAP high-intensity staining in the cytoplasm but not in the nucleus decreases the risk for breast cancer. In conclusion, our overall data suggest that YAP may act as a tumor suppressor protein because their reduced expression in cases, which can induce an environment favorable for inhibition of apoptosis and promoting cellular proliferation by increasing genetic instability of cells, which might contribute to the pathogenesis of cancer. Copyright © 2017 John Wiley & Sons, Ltd.
Hippo 通路调节细胞增殖和凋亡，已有研究指出该通路关键成分的缺失可导致不受控制的细胞生长。Yes 相关蛋白（YAP）是 Hippo 通路的重要组成部分，因为 YAP 是 Hippo 肿瘤抑制通路的核效应物，其对细胞过程和不同外源性化学物质（包括砷）诱导的氧化应激的反应至关重要。已有研究提出 YAP 失调可导致恶性细胞表型，作为肿瘤抑制因子和癌基因发挥作用。本研究旨在评估和比较长期通过饮用水暴露于砷的女性的乳腺肿瘤组织和非肿瘤组织中 YAP 的表达情况。采用免疫组织化学方法检测 120 例乳腺癌患者和 120 例非肿瘤性乳腺病变患者的 YAP 表达情况。并对尿液中的砷浓度进行定量分析。结果显示，病例组中细胞质 YAP 表达的百分比显著降低，且细胞质中 YAP 高表达强度（而非核内）可降低乳腺癌风险。综上，我们的整体数据表明，YAP 可能作为一种肿瘤抑制蛋白发挥作用，因为其在病例组中的低表达可诱导有利于抑制细胞凋亡和促进细胞增殖的环境，从而增加细胞的遗传不稳定性，这可能有助于癌症的发病机制。版权所有©2017 约翰威立父子公司
