The influence of stress on the development and progression of cancer has been a longstanding hypothesis. Chronic stress can have a significant impact on the immune system and inflammatory response, potentially leading to decline of the body's immune capabilities (Segerstrom & Miller, 2004). Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, which triggers the release of stress hormones, such as cortisol (Smith & Vale, 2006). When chronically activated, this can lead to corresponding changes in the immune system, including decreased activity of natural killer cells, which play a crucial role in identifying and destroying cancer cells. Chronic inflammation has also been shown to promote the growth and metastasis of cancer cells and it can also damage DNA, leading to mutations that can contribute to carcinogenesis (Singh et al., 2019).
While it’s clear that chronic stress can have a negative impact on the immune system and inflammatory response and may also play an important role in cancer pathology, the mechanisms remain unclear. The tumor suppressor gene (TP53) encodes a protein called p53, which is a key modulator in the innate and adaptive immune system and is the most frequently mutated gene in cancer (Hernandez Borrero & El-Deiry, 2021). The phosphatase and tensin homolog (PTEN) gene provides instructions for producing an enzyme found in almost all tissues in the body. The enzyme acts as a tumor suppressor and is one of the p53 outputs mediating proliferation. Murine Double Minute 2 (MDM2) is a proto-oncogene that forms a negative feedback loop with p53 and acts as a negative regulator. The overexpression of MDM2 inhibits p53 expression. Here, we examine the role of chronic stress on carcinogenesis through a loss or attenuation of p53 in mouse astrocytes lacking the functional TP53 gene. To investigate this, we focus on corticosterone (main corticosteroid hormone in mice) and a select number of genes, TP53, MDM2, and PTEN. We hypothesize that chronic stress, modeled in this study by prolonged exposure to corticosterone, promotes downregulation of proteins in the p53 regulatory pathway.
Dean, Jillian R., "Examining the Role of Chronic Stress in Cancer Progression and Metastasis: p53 as a Potential Mechanism" (2023). Behavioral Neuroscience Honors Papers. 15.
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The views expressed in this paper are solely those of the author.