Stress‐induced changes in gene expression associated with prostate cancer

Abstract

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