Institute of Nutrition and Food Technology (INTA), Macul, University of Chile, Santiago, Chile.
Gynecol Oncol. 2010 Apr;117(1):96-102. doi: 10.1016/j.ygyno.2009.12.022. Epub 2010 Jan 13.
To examine whether overweight and obesity could lead to increased endometrial proliferation and activation of AKT and ERK1,2 in cycling premenopausal women.
Endometrial and blood samples were obtained from women with normal endometrial histology, and allocated into three groups-normal-weight, overweight and obese-according to the subject's body mass index (BMI). Samples from obese patients with type-I endometrial cancer (EC) were included as a control. Cell proliferation was measured by immunohistochemical detection of Ki67 and phosphorylated histone H3 (p-H3). AKT and ERK1,2 activation was assessed by Western blot. Circulating steroids, leptin and insulin were measured by immunoassays.
In endometrial samples with normal histology, epithelial cell proliferation was higher in the overweight and obese groups versus the normal-weight set (P<0.05). Proliferation indexes were positively correlated with the subject's BMI and serum levels of estrogen, leptin and insulin (P<0.05). Increased phosphorylated AKT (pAKT) (1.6-fold) and ERK1,2 (pERK1,2) (8.7-fold) were observed in endometria from obese with respect to normal-weight subjects (P<0.05). Similarly, increased phosphorylation of AKT (0.7-fold) and ERK1,2 (2.3-fold) was detected in endometria from overweight as compared with the normal-weight group (P<0.05). In women with EC, we found a significant increase in endometrial proliferation, and in pAKT and pERK1,2 expression levels when compared to patients with normal endometrial histology.
These results show correlation between obesity (and overweight) and increased endometrial cell proliferation, and the activation of AKT and ERK1,2. These features could be related with the higher risk to develop type-I EC in overweight and obese women.
研究超重和肥胖是否会导致绝经前循环期女性子宫内膜增殖和 AKT 及 ERK1,2 的激活。
根据受试者的体重指数（BMI），将具有正常子宫内膜组织学的女性子宫内膜和血液样本分为正常体重、超重和肥胖三组。将肥胖Ⅰ型子宫内膜癌（EC）患者的样本纳入对照组。通过 Ki67 和磷酸化组蛋白 H3（p-H3）的免疫组织化学检测来测量细胞增殖。通过 Western blot 评估 AKT 和 ERK1,2 的激活。通过免疫测定测量循环类固醇、瘦素和胰岛素。
在正常组织学的子宫内膜样本中，与正常体重组相比，超重和肥胖组的上皮细胞增殖更高（P<0.05）。增殖指数与受试者的 BMI 以及血清雌激素、瘦素和胰岛素水平呈正相关（P<0.05）。与正常体重组相比，肥胖组的 AKT（pAKT）（1.6 倍）和 ERK1,2（pERK1,2）（8.7 倍）的磷酸化增加（P<0.05）。与正常体重组相比，超重组的 AKT（0.7 倍）和 ERK1,2（2.3 倍）的磷酸化也增加（P<0.05）。与具有正常子宫内膜组织学的患者相比，在患有 EC 的女性中，我们发现子宫内膜增殖、pAKT 和 pERK1,2 表达水平显著增加。
这些结果表明肥胖（和超重）与子宫内膜细胞增殖增加以及 AKT 和 ERK1,2 的激活之间存在相关性。这些特征可能与超重和肥胖女性发生Ⅰ型 EC 的风险增加有关。
