Stress alters the expression of cancer-related genes in the prostate

Abstract

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.

miR-138-5p inhibits the malignant progression of prostate cancer by targeting FOXC1

“…Nowadays, the understanding of the pathogenesis and biological behavior of PCa still has great limitations [8,9]. The development of PCa is a multi-factors process, in uenced by a variety of biomolecules and regulated by signaling pathways [11,12]. With the progress of the Human Genome Project, most researches on molecular and cellular pathobiology have been extensively conducted to detect the differential expression pro le of tumor genes, which is of great signi cance for exploring the molecular mechanism of PCa, and nding the molecular biomarkers in the early diagnosis and prognosis of PCa [13,14].…”

“…Although PSA test greatly improved the early-stage diagnostic rate of PCa, its bene t in decreasing the mortality of PCa remained controversial [9,10]. Like other malignancies, the malignant progress of PCa is a multi-step and multi-stage process, including inactivation of anti-oncogenes and/or activation of proto-oncogenes [11,12]. Currently, the target therapy based on cancer-related miRNAs presented a promising application, and the results of these studies showed that miRNA had a good application prospect in the diagnosis, treatment, prognosis and other aspects of cancer, to provide new ideas for the pathogenesis of PCa [13,14].…”

miR-138-5p inhibits the metastasis of prostate cancer by targeting FOXC1

“…Nowadays, the understanding of the pathogenesis and biological behavior of PCa still has great limitations [8,9]. The development of PCa is a multi-factors process, influenced by a variety of biomolecules and regulated by signaling pathways [11,12]. With the progress of the Human Genome Project, researches on molecular level have been extensively conducted to detect the differential expression profile of tumor genes, which is of great significance for exploring the molecular mechanism of the development of PCa, and finding the molecular biomarkers in the early diagnosis and prognosis of PCa [13,14].…”

“…Although PSA test greatly improves the early-stage diagnostic rate of PCa, its benefit in decreasing the mortality of PCa remains controversial [9,10]. Like other malignancies, the malignant progress of PCa is a multi-step and multi-stage process, including inactivation of tumor suppressor genes and/or activation of proto-oncogenes [11,12]. Currently, target therapy based on tumor-related miRNAs presents a promising application, and the results of these studies showed that miRNA had a good application prospect in the diagnosis, treatment, prognosis and other aspects of cancer, to provide new ideas for the pathogenesis of PCa [13,14].…”

miR-138-5p inhibits the metastasis of prostate cancer by targeting FOXC1

“…Although PSA test greatly improves the early-stage diagnostic rate of PCa, its bene t in decreasing the mortality of PCa remains controversial [9,10]. Like other malignancies, the malignant progress of PCa is a multi-step and multi-stage process, including inactivation of tumor suppressor genes and/or activation of protooncogenes [11,12]. Currently, target therapy based on cancer-related miRNAs presented a promising application, and the results of these studies showed that miRNA had a good application prospect in the diagnosis, treatment, prognosis and other aspects of cancer, to provide new ideas for the pathogenesis of PCa [13,14].…”