ECRG4 expression in normal rat tissues: expression study and literature review

Abstract

The <em>Esophageal Cancer Related Gene 4</em> (<em>ECRG4</em>) is a highly conserved tumour suppressor gene encoding various peptides (augurin, CΔ16 augurin, ecilin, argilin, CΔ16 argilin) which can be processed and secreted. In the present work, we examined <em>ECRG4</em> expression and location in a wide range of rat organs and reviewed the available literature. <em>ECRG4</em> mRNA was identified in all examined tissues by quantitative PCR (qPCR). <em>ECRG4</em> immunoreaction was mainly cytoplasmic, and was detected in heart and skeletal muscles, smooth muscle cells showing only weak reactions. In the digestive system, <em>ECRG4</em> immunostaining was stronger in the esophageal epithelium, bases of gastric glands, hepatocytes and pancreatic acinar epithelium. In the lymphatic system, immunoreactive cells were detectable in the thymus cortex, lymph node medulla and splenic red pulp. In the central and peripheral nervous systems, different neuronal groups showed different reaction intensities. In the endocrine system, <em>ECRG4</em> immunoreaction was detected in the hypothalamic paraventricular and supraoptic nuclei, hypophysis, thyroid and parathyroid glands, adrenal <em>zona glomerularis</em> and medulla and Leydig cells, as well as in follicular and luteal cells of the ovary. In the literature, ECRG4 has been reported to inhibit cell proliferation and increase apoptosis in various cell types. It is down-regulated, frequently due to hypermethylation, in esophageal, prostate, breast and colon cancers, together with glioma (oncosuppressor function), although it is up-regulated in papillary thyroid cancer (oncogenic role). <em>ECRG4</em> expression is also higher in non-proliferating cells of the lymphatic system. In conclusion, our identification of <em>ECRG4</em> in many structures suggests the involvement of <em>ECRG4</em> in the tumorigenesis of other organs and also the need for further research. In addition, on the basis of the location of <em>ECRG4</em> in neurons and endocrine cells and the fact that it can be secreted, its role as a neurotransmitter/neuromodulator and endocrine factor must be examined in depth in the future.