Body fatness and mTOR pathway activation of breast cancer in the Women's Circle of Health Study.
Body fatness and mTOR pathway activation of breast cancer in the Women's Circle of Health Study.
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DOI：
10.1038/s41523-020-00187-4
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发表时间：
2020
影响因子：
5.9
通讯作者：
Ambrosone CB
中科院分区：
文献类型：
--
作者：
Cheng TD;Omilian AR;Yao S;Sanchez PV;Polk LZ;Zhang W;Datta S;Bshara W;Ondracek RP;Davis W;Liu S;Hong CC;Bandera EV;Khoury T;Ambrosone CB
能量失衡在乳腺癌预后中起重要作用。雷帕霉素靶点（mTOR）通路的过度活跃机制与乳腺肿瘤生长相关，但体脂与乳腺癌中mTOR通路活性的相关程度尚不清楚。我们对来自590名妇女（464名非洲裔美国人/黑人和126名白人）的肿瘤组织中的mTOR、磷酸化（p）-mTOR、p-AKT和p-p70 S6 K进行了免疫染色，这些妇女在妇女健康研究圈中患有新诊断的浸润性乳腺癌。由研究人员进行人体测量，并通过生物电阻抗分析测量身体成分。使用线性回归来估计体重指数（BMI）、腰围、腰/臀比、脂肪量、脂肪量指数和体脂百分比类别之间蛋白质表达的百分比差异。我们观察到BMI ≥ 35.0与<25 kg/m2相比，p-mTOR和标准化p-mTOR的表达分别高出108.3%（95% CI = 16.9%-270.9%）和101.8%（95% CI = 17.0%-248.8%），即，p-mTOR/mTOR。腰/臀比为4比1的四分位数与mTOR表达增加41.8%（95%CI = 5.81%-89.9%）相关。在体脂测量中观察到类似的关联，特别是在雌激素受体阴性（ER-）肿瘤患者中，但在ER+肿瘤患者中没有观察到，尽管关联差异不显著。这项基于肿瘤的研究发现，在乳腺癌中，身体肥胖和mTOR通路激活之间存在正相关，这一点通过p-mTOR表达而得到证实。我们的研究结果表明，mTOR抑制可以成为预防肥胖患者这些肿瘤复发的治疗策略。
Energy imbalance has an important role in breast cancer prognosis. Hyperactive mechanistic Target of Rapamycin (mTOR) pathway is associated with breast tumor growth, but the extent to which body fatness is associated with mTOR pathway activities in breast cancer is unclear. We performed immunostaining for mTOR, phosphorylated (p)-mTOR, p-AKT, and p-p70S6K in tumor tissue from 590 women (464 African Americans/Blacks and 126 Whites) with newly diagnosed invasive breast cancer in the Women’s Circle of Health Study. Anthropometric measures were taken by study staff, and body composition was measured by bioelectrical impedance analysis. Linear regressions were used to estimate percent differences in protein expression between categories of body mass index (BMI), waist circumference, waist/hip ratio, fat mass, fat mass index, and percent body fat. We observed that BMI ≥ 35.0 vs. <25 kg/m2 was associated with 108.3% (95% CI = 16.9%–270.9%) and 101.8% (95% CI = 17.0%–248.8%) higher expression in p-mTOR and normalized p-mTOR, i.e., p-mTOR/mTOR, respectively. Quartiles 4 vs. 1 of waist/hip ratio was associated with 41.8% (95% CI = 5.81%–89.9%) higher mTOR expression. Similar associations were observed for the body fat measurements, particularly in patients with estrogen receptor-negative (ER−) tumors, but not in those with ER+ tumors, although the differences in associations were not significant. This tumor-based study found positive associations between body fatness and mTOR pathway activation, evident by a p-mTOR expression, in breast cancer. Our findings suggest that mTOR inhibition can be a treatment strategy to prevent the recurrence of these tumors in obese individuals.