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      Social isolation induces autophagy in the mouse mammary gland: link to increased mammary cancer risk

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          Abstract

          Social isolation is a strong predictor of early all-cause mortality and consistently increases breast cancer risk in both women and animal models. Because social isolation increases body weight, we compared its effects to those caused by a consumption of obesity-inducing diet (OID) in C57BL/6 mice. Social isolation and OID impaired insulin and glucose sensitivity. In socially isolated, OID-fed mice (I-OID), insulin resistance was linked to reduced Pparg expression and increased neuropeptide Y levels, but in group-housed OID fed mice (G-OID), it was linked to increased leptin and reduced adiponectin levels, indicating that the pathways leading to insulin resistance are different. Carcinogen-induced mammary tumorigenesis was significantly higher in I-OID mice than in the other groups, but cancer risk was also increased in socially isolated, control diet-fed mice (I-C) and G-OID mice compared with that in controls. Unfolded protein response (UPR) signaling (GRP78; IRE1) was upregulated in the mammary glands of OID-fed mice, but not in control diet-fed, socially isolated I-C mice. In contrast, expression of BECLIN1, ATG7 and LC3II were increased, and p62 was downregulated by social isolation, indicating increased autophagy. In the mammary glands of socially isolated mice, but not in G-OID mice, mRNA expressions of p53 and the p53-regulated autophagy inducer Dram1 were upregulated, and nuclear p53 staining was strong. Our findings further indicated that autophagy and tumorigenesis were not increased in Atg7 +/− mice kept in social isolation and fed OID. Thus, social isolation may increase breast cancer risk by inducing autophagy, independent of changes in body weight.

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          Most cited references71

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          Social Isolation in America: Changes in Core Discussion Networks over Two Decades

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            Development by Self-Digestion

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              Social isolation: a predictor of mortality comparable to traditional clinical risk factors.

              We explored the relationship between social isolation and mortality in a nationally representative US sample and compared the predictive power of social isolation with that of traditional clinical risk factors.
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                Author and article information

                Journal
                Endocrine-Related Cancer
                Bioscientifica
                1351-0088
                1479-6821
                October 2016
                October 2016
                October 2016
                October 2016
                : 23
                : 10
                : 839-856
                Article
                10.1530/ERC-16-0359
                5894876
                27550962
                44de859a-ca20-4e09-a875-7b7b24d3568c
                © 2016

                Free to read

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