流行病學研究已經(jīng)表明,慢性心理壓力能夠促進腫瘤發(fā)生。然而在體內(nèi)，慢性心理壓力與腫瘤發(fā)生之間的聯(lián)系以及潛在的機制還不明確,。
近日，美國新澤西醫(yī)科和牙科大學的研究人員對此開展了一項研究，該研究對慢性壓力能夠促進體內(nèi)腫瘤發(fā)生提供了直接證據(jù),。相關(guān)論文發(fā)表在5月1的PNAS上。
研究發(fā)現(xiàn),，在已建立的老鼠模型中,，慢性束縛顯著促進了電離輻射(IR)誘導(dǎo)的腫瘤生成。
腫瘤抑制蛋白p53在腫瘤抑制中起著極其重要的作用,，而p53功能的失去或是弱化則會促進腫瘤發(fā)生,。
研究發(fā)現(xiàn)，慢性束縛降低了老鼠p53的水平并弱化其功能,，促進了人類異種移植腫瘤的生長,。
該研究表明,，當慢性束縛介導(dǎo)對p53的作用時，通過誘導(dǎo)血清和糖皮質(zhì)激素誘導(dǎo)激酶（SGK1）,，糖皮質(zhì)激素水平升高,，這反過來提高MDM2的活性，降低p53的功能,。
總的來說,，該研究闡明了慢性束縛促進老鼠腫瘤發(fā)生的機制，對腫瘤發(fā)生有關(guān)研究提供了更多的思路,。（生物谷Deepblue編譯）
doi: 10.1073/pnas.1203930109
PMC:
PMID:
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.
