Cancer related gene expression in the human prostate zones

The normal prostate: The prostate is the largest accessory gland of the male reproductive system. (Figure 1) The healthy adult prostate is about the size of a chestnut and conical in shape. In general, it measures 20 ml in volume, though it can become five or six time that size with increasing age. The prostate is shaped like an inverted pyramid and lies between the bladder and the pelvic floor (1). The prostate supplies about 30% of the volume of the seminal fluid. The normal prostate is composed of epithelial glands and stroma. These glands represent the terminal tubular portion of long tubulo-alveolar glands that radiate from the urethra. The glands are lined by two cell layers: an outer low cuboidal layer and an inner layer of tall columnar mucin-secreting epithelium. Half of the volume of the prostate is occupied by the fibromuscular stroma between the glands. The prostate zones: The prostate consist of several zones, the peripheral zone, the central zone and the transition zone (Figure 2). Prostate cancer mainly occurs in peripheral zone, whereas benign prostatic hyperplasia (BPH) merely occurs in transition zone. BPH is a benign enlargement of the prostate

The FOXF2 Pathway in the Human Prostate Stroma

BACKGROUND. Forkhead box 2 (FOXF2) is a member of the large family of forkhead transcription factors and its expression pattern suggests a role in prostate cancer development. FOXF2 expression is stroma-specific and higher expressed in the prostate transition zone than the prostate peripheral zone. Moreover, expression of FOXF2 is decreased in prostate cancer. METHODS. To identify the genes and pathways regulated by FOXF2, we compared microarray expression profiles of primary prostate stromal cells (PrSC) treated with control or small interfering RNA (siRNA) directed against FOXF2. RESULTS. From our microarray analyses, we selected 190 differentially expressed genes, of which 104 genes were higher expressed in PrSC cells treated with FOXF2 siRNA and 86 were higher expressed in PrSC cells treated with negative control siRNA. Eight of the strongest differentially expressed genes were validated by RT-PCR. Genes down-regulated by FOXF2 included MT1E, MT1F, PDGFA, ITGB1, and PSG7 and genes up-regulated by FOXF2 included WASF2, BAMBI, and CXCL12. Ingenuity pathway analysis showed several pathways significantly regulated by FOXF2, including PPAR signaling, PDGF signaling, and extracellular matrix (ECM) signaling. GSEA analysis revealed that FOXF2 up-regulated genes were down-regulated in the same PrSC cells treated with transforming growth factor 3 (TGF beta 3). CONCLUSIONS. The distinct expression pattern of FOXF2 in the prostate, its effect on expression of ECM signaling, and its opposing role in the TGF beta 3 pathway, suggests a role for FOXF2 in prostate homeostasis and stroma-epithelial interactions. Prostate 69: 1538-1547, 2009. (C) 2009 Wiley-Liss, Inc

An Inflammatory Gene-Expression Fingerprint in Monocytes of Autoimmune Thyroid Disease Patients

Context: In monocytes of patients with autoimmune diabetes, we recently identified a gene expression fingerprint of two partly overlapping gene clusters, a PDE4B-associated cluster (consisting of 12 core proinflammatory cytokine/compound genes), a FABP5-associated cluster (three core genes), and a set of nine overlapping chemotaxis, adhesion, and cell assembly genes correlating to both PDE4B and FABP5. Objective: Our objective was to study whether a similar monocyte inflammatory fingerprint as found in autoimmune diabetes is present in autoimmune thyroid disease (AITD). Design and Patients: Quantitative PCR was used for analysis of 28 genes in monocytes of 67 AITD patients and 70 healthy controls. The tested 28 genes were the 24 genes previously found abnormally expressed in monocytes of autoimmune diabetes patients plus four extra genes found in whole-genome analysis of monocytes of AITD patients reported here. Results: Monocytes of 24% of AITD and 50% of latent autoimmune diabetes of adults (LADA) patients shared an inflammatory fingerprint consisting of the set of 24 genes of the PDE4B, FABP5, and overlapping gene sets. This study in addition revealed that FCAR, the gene for the Fc alpha receptor I, and PPBP, the gene for CXCL7, were part of this proinflammatory monocyte fingerprint. Conclusions: Our study provides an important tool to determine a shared, specific proinflammatory state of monocytes in AITD and LADA patients, enabling further research into the role of such proinflammatory cells in the failure to preserve tolerance in these conditions and of key fingerprint genes involved. (J Clin Endocrinol Metab 95: 1962-1971, 2010

The mononuclear phagocyte system and its cytokine inflammatory networks in schizophrenia and bipolar disorder

This review describes patients with schizophrenia and bipolar disorder. In such patients, a high inflammatory set point of circulating monocytes at the transcriptome level is observed, involving various inflammatory transcripts forming distinct fingerprints (the transcriptomic monocyte fingerprint in schizophrenia overlaps with that in bipolar disorder, but also differs with it at points). There are increased levels of compounds of the IL-1, IL-6 and TNF system in the serum (be it modest and inconsistent). There is also evidence that the IL-2 system is activated in patients with schizophrenia (and perhaps those with mania), although independently of the activation of the IL-1, IL-6 and TNF systems, suggesting separate inducing mechanisms for monocyte and T-cell activation. It is not yet known whether such T cell activation involves the Th1/Th2/Th17 or Treg systems