流行病学研究已经表明,慢性心理压力能够促进肿瘤发生。然而在体内，慢性心理压力与肿瘤发生之间的联系以及潜在的机制还不明确。
近日，美国新泽西医科和牙科大学的研究人员对此开展了一项研究，该研究对慢性压力能够促进体内肿瘤发生提供了直接证据。相关论文发表在5月1的PNAS上。
研究发现，在已建立的老鼠模型中，慢性束缚显著促进了电离辐射(IR)诱导的肿瘤生成。
肿瘤抑制蛋白p53在肿瘤抑制中起着极其重要的作用，而p53功能的失去或是弱化则会促进肿瘤发生。
研究发现，慢性束缚降低了老鼠p53的水平并弱化其功能，促进了人类异种移植肿瘤的生长。
该研究表明，当慢性束缚介导对p53的作用时，通过诱导血清和糖皮质激素诱导激酶（SGK1），糖皮质激素水平升高，这反过来提高MDM2的活性，降低p53的功能。
总的来说，该研究阐明了慢性束缚促进老鼠肿瘤发生的机制，对肿瘤发生有关研究提供了更多的思路。（生物谷Deepblue编译）
doi: 10.1073/pnas.1203930109
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Chronic restraint stress attenuates p53 function and promotes tumorigenesis
Zhaohui Feng, Lianxin Liu, Cen Zhang, Tongsen Zheng, Jiabei Wang, Meihua Lin, Yuhan Zhao, Xiaowen Wang, Arnold J. Levine, and Wenwei Hu.
Epidemiological studies strongly suggest that chronic psychological stress promotes tumorigenesis. However, its direct link in vivo and the underlying mechanisms that cause this remain unclear. This study provides direct evidence that chronic stress promotes tumorigenesis in vivo; chronic restraint, a well-established mouse model to induce chronic stress, greatly promotes ionizing radiation (IR)-induced tumorigenesis in p53+/- protein p53 plays a central role in tumor prevention. Loss or attenuation of p53 function contributes greatly to tumorigenesis. We found that chronic restraint decreases the levels and function of p53 in mice, and furthermore, promotes the growth of human xenograft tumors in a largely p53-dependent manner.Our results show that glucocorticoids elevated during chronic restraint mediate the effect of chronic restraint on p53 through the induction of serum- and glucocorticoid-induced protein kinase (SGK1), which in turn increases MDM2 activity and decreases p53 function.Taken together, this study demonstrates that chronic stress promotes tumorigenesis in mice, and the attenuation of p53 function is an important part of the underlying mechanism, which can be mediated by glucocortcoids elevated during chronic restraint.
