BackgroundProstate cancer is a major contributor to mortality worldwide, and significant efforts are being undertaken to decipher specific cellular and molecular pathways underlying the disease. Chronic stress is known to suppress reproductive function and promote tumor progression in several cancer models, but our understanding of the mechanisms through which stress contributes to cancer development and progression is incomplete. We therefore examined the relationship between stress, modulation of the gonadotropin-releasing hormone (GnRH) system, and changes in the expression of cancer-related genes in the rat prostate.MethodsAdult male rats were acutely or repeatedly exposed to restraint stress, and compared to unstressed controls and groups that were allowed 14 days of recovery from the stress. Prostate tissue was collected and frozen for gene expression analyses by PCR array before the rats were transcardially perfused; and brain tissues harvested and immunohistochemically stained for Fos to determine neuronal activation.ResultsAcute stress elevated Fos expression in the paraventricular nucleus of the hypothalamus (PVH), an effect that habituated with repeated stress exposure. Data from the PCR arrays showed that repeated stress significantly increases the transcript levels of several genes associated with cellular proliferation, including proto-oncogenes. Data from another array platform showed that both acute and repeated stress can induce significant changes in metastatic gene expression. The functional diversity of genes with altered expression, which includes transcription factors, growth factor receptors, apoptotic genes, and extracellular matrix components, suggests that stress is able to induce aberrant changes in pathways that are deregulated in prostate cancer.ConclusionsOur findings further support the notion that stress can affect cancer outcomes, perhaps by interfering with neuroendocrine mechanisms involved in the control of reproduction.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3635-4) contains supplementary material, which is available to authorized users.

Prostate cancer is common among men in the U.S., and stress is prevalent in our society, but the relationship between stress and prostate cancer is not well defined. Stress modulation of the gonadotropin‐releasing hormone (GnRH) system, and the use of GnRH analogs in prostate cancer treatment, suggests this endocrine pathway as a possible link between these two conditions. In this study, our hypothesis was that stress would suppress GnRH and increase the expression of proliferation‐associated genes in prostate tissue. Adult male rats were acutely (30min × 1d) or repeatedly (30min × 21d) restrained and prostate tissues analyzed by PCR array to determine changes in cancer‐related gene expression. Acute and repeated stress caused significant (p<0.05) downregulation of different genes associated with cellular proliferation. Angiopoeitin‐2 and cadherin‐2 were reduced by acute stress, while caspase‐2 and ‐7, IGF binding protein‐3 and ‐7, and MAPKK1 were decreased following repeated stress. Telomerase‐associated protein‐1 was significantly decreased by both stress treatments. These data demonstrate that expression of genes involved in proliferation is downregulated in prostate tissue from stressed animals. Our findings may help identify biomarkers for prostate cancer, and mechanisms through which stress may contribute to prostate cancer progression.Support: 5U54RR022762–03S1, 8G12MD007592