Heublein Sabine, Vrekoussis Thomas, Etzl Ronny, Rotzoll Daisy, Kuhn Christina, Faigle Gesine, Navrozoglou Iordanis, Stefos Theodore, Makrigiannakis Antonis, Jeschke Udo
Department of Obstetrics and Gynecology, Ludwig Maximilians University, Munich, Germany.
Department of Obstetrics and Gynecology, Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany.
J Cancer Res Clin Oncol. 2017 May;143(5):773-781. doi: 10.1007/s00432-017-2340-7. Epub 2017 Feb 17.
Increased oxidative stress plays an important role in cancer development. Vitamin E is considered a potent anti-oxidant and its transfer protein αTTP facilitates its cellular delivery. We hypothesize that αTTP could be present in and have an impact on endometrial cancer.
Ishikawa endometrial cancer cells were treated with BSO and AAPH to mimick oxidative stress conditions. αTTP was detected by immunocytochemistry and western blot. αΤΤP expression was then assessed in 191 endometrioid endometrial carcinomas. Immunopositivity was correlated with grade, FIGO stage, and 5-year survival. Immuno-reactivity was assessed with a semi-quantitative score.
AAPH- and BSO-induced αTTP expression in Ishikawa cells. Immunohistochemical assessment of the 191 endometrial cancer cases showed that αTTP expression correlated with FIGO stage (p = 0.014) but not with grade. Five-year survival was significantly better in cases of lower αTTP expression compared to cases with higher expression (p = 0.041).
The current results show that αTTP plays a role in endometrial carcinoma. Possibly endometrial cancer cells attempt to protect themselves from increasing oxidative stress by up-regulating αTTP. Selective molecular interventions targeting oxidative stress escape strategies, e.g., by overexpression of αTTP, could, therefore, allow oxidative stress to damage cancer cell membranes and thus restrict cancer progression.
氧化应激增加在癌症发展中起重要作用。维生素E被认为是一种有效的抗氧化剂，其转运蛋白αTTP促进其细胞内递送。我们假设αTTP可能存在于子宫内膜癌中并对其产生影响。
用BSO和AAPH处理 Ishikawa子宫内膜癌细胞以模拟氧化应激条件。通过免疫细胞化学和蛋白质印迹法检测αTTP。然后在191例子宫内膜样腺癌中评估αTTP表达。免疫阳性与分级、国际妇产科联盟（FIGO）分期和5年生存率相关。用半定量评分评估免疫反应性。
AAPH和BSO诱导Ishikawa细胞中αTTP表达。对191例子宫内膜癌病例的免疫组织化学评估显示，αTTP表达与FIGO分期相关（p = 0.014），但与分级无关。与αTTP高表达病例相比，αTTP低表达病例的5年生存率明显更好（p = 0.041）。
目前的结果表明αTTP在子宫内膜癌中起作用。子宫内膜癌细胞可能试图通过上调αTTP来保护自己免受不断增加的氧化应激。因此，针对氧化应激逃逸策略的选择性分子干预，例如通过αTTP的过表达，可能使氧化应激损伤癌细胞膜，从而限制癌症进展。
