Early Social Enrichment Modulates Tumor Progression and p53 Expression in Adult Mice

Abstract

Epidemiological evidence indicates that stress and aversive psychological conditions can affect cancer progression, while well-being protects against it. Although a large set of studies have addressed the impact of stress on cancer, not much is known about the mechanisms that protect from cancer in healthy psychological conditions. C57BL/6J mouse pups were exposed to an environmental enrichment condition consisting of being raised until weaning by the biological lactating mother plus a non-lactating virgin female (LnL = Lactating and non-Lactating mothers). The Control group consisted of mice raised by a single lactating mother (L = Lactating). Four months after weaning, mice from LnL and L conditions were exposed to intramuscular injection of 3-methylcolantrene (3MCA), a potent tumorigenic drug, and onset and progression of 3MCA-induced fibrosarcomas were monitored over time. Pups from the LnL compared to the L group received more parental care and were more resilient to stressful events during the first week of life. In association, the onset of tumors in LnL adults was significantly delayed. At the molecular level, we observed increased levels of wild-type p53 protein in tumor samples of LnL compared to L adults and higher levels of its target p21 in healthy muscles of LnL mice compared to the L group, supporting the hypothesis of potential involvement of p53 in tumor development. Our study sustains the model that early life care protects against tumor susceptibility.

p53 Function and Dysfunction in Human Health and Diseases

“…Middei et al, using a combination of enrichment conditions and DNA-damage-mediated tumor induction, reported that exposing mice pups to early physical and social enrichment delays tumor progression in adulthood. In agreement with these results on a molecular level, the authors observed increased p53 activity in healthy tissue and decreased levels of Mdm2, the main inhibitor of p53, suggesting that early social enrichment can antagonize DNA-damage-induced tumorigenesis in mice with the possible involvement of p53 activity [ 19 ]. These findings are in line with a set of studies demonstrating that exposure to protective factors can drive persistent changes in molecular pathways, which are sufficient to trigger anti-tumoral responses upon carcinogenic insult [ 20 ].…”