Department of Toxicology, Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul, Korea.
Department of Otolaryngology, Hanyang University College of Medicine, Seoul, Korea.
Cancer Res Treat. 2018 Jan;50(1):111-117. doi: 10.4143/crt.2017.001. Epub 2017 Mar 8.
For the target treatment and prevention of women's increased thyroid cancer, we focused on risks of environmental exposure to endocrine disrupting chemicals, particularly bisphenol A (BPA), and its high susceptible exposure-timing, particularly early exposure in lives.
Female ICR mice were exposed to BPA and in early life (15, 75, and 300 mg/L of drinking water via pregnant mice and lactation). We identified BPA-responsive proteins in mice thyroid by two-dimensional gel electrophoresis, image analyses, and electrospray ionization quadrupole time-of-flight mass spectrometry. We further analyzed expression of the BPA-responsive proteins in women thyroid cancer patients (n=28).
We found the altered 17 proteins in BPA dose-dependent manner among the thyroid tissues of offspring mice and identified nine proteins of them, including Anxa6, Atp5b, Hspa5, and Vcp, etc. In addition, we observed the positive association between blood BPA levels and mRNA expression of the and not in normal but thyroid cancer tissues.
Our study provides ANXA6 and VCP as proteomic biomarkers for BPA-early life exposure and their potential for women's thyroid cancer.
为了针对女性甲状腺癌发病率上升的情况进行靶向治疗和预防，我们重点研究了环境内分泌干扰化学物质（特别是双酚 A，BPA）暴露风险，尤其是生命早期的高敏感暴露时机。
通过给怀孕母鼠和哺乳期母鼠喂以含不同剂量（15、75 和 300mg/L）BPA 的饮用水，使雌性 ICR 小鼠接触 BPA。我们通过二维凝胶电泳、图像分析和电喷雾电离四极杆飞行时间质谱分析，鉴定了小鼠甲状腺中的 BPA 反应蛋白。然后，我们进一步分析了 28 例女性甲状腺癌患者的甲状腺组织中 BPA 反应蛋白的表达情况。
我们发现，BPA 可使子代小鼠甲状腺组织中的 17 种蛋白发生剂量依赖性改变，其中包括 Anxa6、Atp5b、Hspa5 和 Vcp 等 9 种蛋白。此外，我们观察到血液中 BPA 水平与 和 在甲状腺癌组织中的 mRNA 表达呈正相关，但在正常甲状腺组织中则无此相关性。
本研究为 BPA 早期暴露提供了 ANXA6 和 VCP 作为蛋白质组学生物标志物，提示它们可能与女性甲状腺癌相关。
