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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors
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Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors

机译：社会隔离失调内分泌和行为压力，同时增加自发性乳腺肿瘤的恶性负担

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摘要

In a life span study, we examined how the social environment regulates naturally occurring tumor development and malignancy in genetically prone Sprague-Dawley rats. We randomly assigned this gregarious species to live either alone or in groups of five female rats. Mammary tumor burden among social isolates increased to 84 times that of age-matched controls, as did malignancy, specifically a 3.3 relative risk for ductal carcinoma in situ and invasive ductal carcinoma, the most common early breast cancers in women. Importantly, isolation did not extend ovarian function in late middle age; in fact, isolated animals were exposed to lower levels of estrogen and progesterone in the middle-age period of mammary tumor growth, with unchanged tumor estrogen and progesterone receptor status. Isolates, however, did develop significant dysregulation of cortico-sterone responses to everyday stressors manifest in young adulthood, months before tumor development, and persisting into old age. Among isolates, corticosterone response to an acute stressor was enhanced and recovery was markedly delayed, each associated with increased mammary tumor progression. In addition to being stressed and tumor prone, an array of behavioral measures demonstrated that socially isolated females possessed an anxious, fearful, and vigilant phenotype. Our model provides a framework for studying the interaction of social neglect with genetic risk to identify mechanisms whereby psychosocial stressors increase growth and malignancy of breast cancer.
机译：在一项寿命研究中，我们研究了社交环境如何调节遗传易发的Sprague-Dawley大鼠的自然发生的肿瘤发展和恶性肿瘤。我们随机地将这些群居的物种单独或单独生活在五只雌性大鼠中。社交隔离群中的乳腺肿瘤负担和年龄相匹配的对照相比，增加到了84倍，恶性肿瘤也是如此，特别是女性中最常见的早期乳腺导管癌和浸润性导管癌的相对风险为3.3。重要的是，隔离并不能延长中晚期的卵巢功能。实际上，在乳腺肿瘤生长的中年期，分离出的动物暴露于较低水平的雌激素和孕激素，而肿瘤雌激素和孕激素受体的状态却没有改变。但是，分离物确实在年轻成年，肿瘤发展之前的几个月以及持续到老年时，对日常应激源的皮质类固醇激素反应产生了明显的失调。在分离物中，皮质酮对急性应激源的反应增强，并且恢复显着延迟，每种都与乳腺肿瘤进展增加有关。除了承受压力和易患肿瘤外，一系列行为措施还表明，与社会隔绝的女性具有焦虑，恐惧和警惕的表型。我们的模型提供了一个框架，用于研究社会忽视与遗传风险的相互作用，从而确定心理社会压力源增加乳腺癌生长和恶性程度的机制。

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    Gretchen L. Hermes; Bertha Delgado; Maria Tretiakova; Sonia A. Cavigelli; Thomas Krausz; Suzanne D. Conzen; Martha K. McClintock;

  • 作者单位

    Institute for Mind and Biology and Departments, The University of Chicago, Chicago, IL 60637 Cornparative Human Development, The University of Chicago, Chicago, IL 60637;

    Institute for Mind and Biology and Departments, The University of Chicago, Chicago, IL 60637 Pathology, The University of Chicago, Chicago, IL 60637;

    Institute for Mind and Biology and Departments, The University of Chicago, Chicago, IL 60637 Pathology, The University of Chicago, Chicago, IL 60637;

    Institute for Mind and Biology and Departments, The University of Chicago, Chicago, IL 60637;

    Institute for Mind and Biology and Departments, The University of Chicago, Chicago, IL 60637 Pathology, The University of Chicago, Chicago, IL 60637;

    Institute for Mind and Biology and Departments, The University of Chicago, Chicago, IL 60637 Medicine, The University of Chicago, Chicago, IL 60637;

    Institute for Mind and Biology and Departments, The University of Chicago, Chicago, IL 60637 Cornparative Human Development, The University of Chicago, Chicago, IL 60637 Psychology, The University of Chicago, Chicago, IL 60637;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    breast cancer; glucocorticoids; physiological stress; psychological stress; social behavior;

    机译：乳腺癌;糖皮质激素;生理压力心理压力社会行为;

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