Division of Cancer Prevention and Control, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
Department of Biostatistics, University of Florida, Gainesville, Florida.
Cancer Res Commun. 2023 Mar 7;3(3):395-403. doi: 10.1158/2767-9764.CRC-22-0405. eCollection 2023 Mar.
Physical activity (PA) is associated with decreased signaling in the mTOR pathway in animal models of mammary cancer, which may indicate favorable outcomes. We examined the association between PA and protein expression in the mTOR signaling pathway in breast tumor tissue. Data on 739 patients with breast cancer, among which 125 patients had adjacent-normal tissue, with tumor expression for mTOR, phosphorylated (p)-mTOR, p-AKT, and p-P70S6K were analyzed. Self-reported recreational PA levels during the year prior to diagnosis were classified using the Centers for Disease Control and Prevention guideline as sufficient (for moderate or vigorous) PA or insufficient PA (any PA but not meeting the guideline) or no PA. We performed linear models for mTOR protein and two-part gamma hurdle models for phosphorylated proteins. Overall, 34.8% of women reported sufficient PA; 14.2%, insufficient PA; 51.0%, no PA. Sufficient (vs. no) PA was associated with higher expression for p-P70S6K [35.8% increase; 95% confidence interval (CI), 2.6-80.2] and total phosphoprotein (28.5% increase; 95% CI, 5.8-56.3) among tumors with positive expression. In analyses stratified by PA intensity, sufficient versus no vigorous PA was also associated with higher expression levels of mTOR (beta = 17.7; 95% CI, 1.1-34.3) and total phosphoprotein (28.6% higher; 95% CI, 1.4-65.0 among women with positive expression) in tumors. The study found that guideline-concordant PA levels were associated with increased mTOR signaling pathway activity in breast tumors. Studying PA in relation to mTOR signaling in humans may need to consider the complexity of the behavioral and biological factors.
PA increases energy expenditure and limits energy utilization in the cell, which can influence the mTOR pathway that is central to sensing energy influx and regulating cell growth. We studied exercise-mediated mTOR pathway activities in breast tumor and adjacent-normal tissue. Despite the discrepancies between animal and human data and the limitations of our approach, the findings provide a foundation to study the mechanisms of PA and their clinical implications.
在乳腺癌动物模型中，体力活动（PA）与 mTOR 通路信号的降低有关，这可能表明预后良好。我们研究了 PA 与乳腺癌肿瘤组织中 mTOR 信号通路蛋白表达之间的关系。对 739 名乳腺癌患者的数据进行了分析，其中 125 名患者有相邻正常组织，肿瘤中 mTOR、磷酸化（p）-mTOR、p-AKT 和 p-P70S6K 的表达情况。在诊断前一年，通过美国疾病控制与预防中心的指南，将自我报告的休闲 PA 水平分为足够（中等到剧烈）PA 或不足 PA（任何 PA 但不符合指南）或无 PA。我们对 mTOR 蛋白进行了线性模型分析，对磷酸化蛋白进行了两部分伽马障碍模型分析。总体而言，34.8%的女性报告有足够的 PA；14.2%，不足 PA；51.0%，无 PA。与无 PA 相比，有足够的 PA 与 p-P70S6K 的表达较高相关[35.8%的增加；95%置信区间（CI），2.6-80.2]和肿瘤阳性表达的总磷酸蛋白（28.5%的增加；95%CI，5.8-56.3）。在按 PA 强度分层的分析中，与无剧烈 PA 相比，有足够的剧烈 PA 也与肿瘤中 mTOR（β=17.7；95%CI，1.1-34.3）和总磷酸蛋白（28.6%更高；95%CI，1.4-65.0）的表达水平较高相关，在肿瘤阳性表达的女性中。研究发现，符合指南的 PA 水平与乳腺癌肿瘤中 mTOR 信号通路活性的增加有关。在人类中，研究 PA 与 mTOR 信号之间的关系可能需要考虑行为和生物学因素的复杂性。
PA 增加能量消耗并限制细胞内的能量利用，这可能影响到 mTOR 通路，该通路是感应能量流入和调节细胞生长的核心。我们研究了运动介导的乳腺癌和相邻正常组织中的 mTOR 通路活性。尽管动物和人类数据之间存在差异，并且我们的方法存在局限性，但这些发现为研究 PA 的机制及其临床意义提供了基础。
