Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors

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

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

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 corticosterone responses to everyday stressors manifest in young adulthood, months before tumor development, and persisting into old age.Amongisolates, 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.

Original languageEnglish (US)
Pages (from-to)22393-22398
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number52
DOIs
StatePublished - Dec 19 2009

Keywords

  • Breast cancer
  • Glucocorticoids
  • Physiological stress
  • Psychological stress
  • Social behavior

ASJC Scopus subject areas

  • General

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