title: Increased SNAIL expression and low syndecan levels are associated with high Gleason grade in prostate cancer.
abstract: Prostate cancer (PC) is a leading male oncologic malignancy wideworld. During malignant transformation, normal epithelial cells undergo genetic and morphological changes known as epithelial-mesenchymal transition (EMT). Several regulatory genes and specific marker proteins are involved in PC EMT. Recently, syndecans have been associated with malignancy grade and Gleason score in PC. Considering that SNAIL is mainly a gene repressor increased in PC and that syndecan promoters have putative binding sites for this repressor, we propose that SNAIL might regulate syndecan expression during PC EMT. The aim of this study was to analyze immunochemically the expression of SNAIL, syndecans 1 and 2 and other EMT markers in a tissue microarray (TMA) of PC samples and PC cell lines. The TMAs included PC samples of different Gleason grade and benign prostatic hyperplasia (BPH) samples, as non‑malignant controls. PC3 and LNCaP cell lines were used as models of PC representing different tumorigenic capacities. Semi-quantitative immunohistochemistry was performed on TMAs and fluorescence immunocytochemistry and western blot analysis were conducted on cell cultures. Results show that SNAIL exhibits increased expression in high Gleason specimens compared to low histological grade and BPH samples. Accordingly, PC3 cells show higher SNAIL expression levels compared to LNCaP cells. Conversely, syndecan 1, similarly to E-cadherin (a known marker of EMT), shows a decreased expression in high Gleason grades samples and PC3 cells. Interestingly, syndecan 2 shows no changes associated to histological grade. It is concluded that increased SNAIL levels in advanced PC are associated with low expression of syndecan 1. The mechanism by which SNAIL regulates the expression of syndecan 1 remains to be investigated.
authors.affiliation: Physiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Cristian E
authors.initials: CE
authors.lastname: Poblete
authors.affiliation: Physiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Juan
authors.initials: J
authors.lastname: Fulla
authors.affiliation: Physiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Marcela
authors.initials: M
authors.lastname: Gallardo
authors.affiliation: Physiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Valentina
authors.initials: V
authors.lastname: Muñoz
authors.affiliation: Physiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Enrique A
authors.initials: EA
authors.lastname: Castellón
authors.affiliation: Pathological Anatomy Service, Clinic Hospital, University of Chile, Santiago, Chile.
authors.forename: Ivan
authors.initials: I
authors.lastname: Gallegos
authors.affiliation: Physiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Hector R
authors.initials: HR
authors.lastname: Contreras
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D000071250:Snail Family Transcription Factors; D053668:Syndecan-1 / Q000096:biosynthesis* / Q000378:metabolism; D053669:Syndecan-2 / Q000096:biosynthesis* / Q000378:metabolism; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: C508241:SDC1 protein, human; D000071250:Snail Family Transcription Factors; D053668:Syndecan-1; D014157:Transcription Factors; D053669:Syndecan-2