Indeed, RB18A/MED1 knockdown in melanoma cells in vitro increased their invasive properties, without modification of cell proliferation. Furthermore, RB18A/MED1 knockdown in vivo switched
melanoma phenotype from non- to strongly-tumorigenic in nude mice. Thus, our data demonstrated for the first time that down-expression of RB18A/MED1 in human melanoma cells strongly AZD2014 nmr increases tumor progression by modifications of the tumor microenvironment. Poster No. 10 SNAI1 Expression in Colon Cancer Related with CDH1 and VDR Downregulation in Normal Adjacent Tissue Jose Miguel Garcia 1 , Cristina Peña1, Maria Jesus Larriba2, Vanesa Garcia1, Javier Silva1, Gemma Dominguez1, Rufo Rodriguez3, Antonio Garcia de Herreros4, Jose Ignacio Casal5, Alberto Muñoz2, Felix Bonilla1 1 Deparment of Medical Oncology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain, 2 Instituto de Investigaciones Biomedicas “Alberto Sols”, Consejo Superior de Investigaciones Cientificas-Unoversidad Autonoma
de Madrid, Madrid, Spain, 3 Deparment of pathology, Hospital Virgende la Salud, Toledo, Spain, 4 Unitat de Biologia MX69 in vivo Cellular i Molecular, Institut Municipal D’investigacio ARS-1620 ic50 Medica, Universitat Pompeu Fabra, Barcelona, Spain, 5 Biotechnology Program, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain SNAIL1 (SNAI1), ZEB1, E-cadherin (CDH1) and vitamin D receptor (VDR) genes regulate the epithelial-mesenchymal transition (EMT) that initiates the invasion process of many tumor cells. We hypothesized that this process could also affect the behavior others of normal cells adjacent to the tumor. To verify this hypothesis, the expression level of these genes was determined by quantitative RT-PCR in tumor, normal adjacent and normal distant tissues from 32 colorectal
cancer patients. In addition, we extended the study to human SW480-ADH colon cancer cells co-cultured with derivative cells over-expressing the mouse Snai1 gene. Of 18 CC cases with SNAI1 expression in tumor tissue, 5 also had SNAI1 in normal adjacent tissue. Expression of SNAI1, but not of ZEB1, in tumor tissue correlated with downregulation of CDH1 and VDR genes in both tumor (p = 0.047 and p = 0.014, respectively) and normal adjacent tissue lacking SNAI1 expression (p = 0.054 and p = 0.003). ZEB1 expression was directly related to VDR expression in tumor tissue (r = 0.39; p = 0.027) and inversely to CDH1 in normal adjacent tissue (r = −0.46; p = 0.010). CDH1 was also downregulated in SW480-ADH cells co-cultured with Snai1-expressing cells. Furthermore, proteomic analysis showed differences in the conditioned media obtained from the two cell types.