4487

MSX1

HOX7|HYD1|STHAG1;msh homeobox 1;MSX1;msh homeobox 1

homeobox 7|homeobox protein Hox-7|homeobox protein MSX-1|msh homeo box 1|msh homeobox 1-like protein|msh homeobox homolog 1

4p16.2

protein-coding

Neuroblastoma is the most common extra-cranial solid childhood cancer; it arisesfrom neural crest-derived cells of the sympathetic nervous system. The anomalousregulation of embryonic developmental pathways like Delta-Notch and Wnt has beenimplicated in aberrant cell growth and differentiation in many (childhood) tumours. We have previously found regulation of Delta-Notch pathway genes by theMSX1 neural crest development gene in a neuroblastoma cell line, and significantcorrelations between these genes in neuroblastic tumours. However, a clear role for the Wnt pathway in neuroblastic tumours has not yet been determined. We now analyze the complete spectrum of genes regulated by inducible expression of MSX1in the SJNB8 neuroblastoma cell line using Affymetrix expression profiling. We show that MSX1 induces the expression of four different Wnt pathway inhibitor genes: Dickkopf 1-3 (DKK1-3) and secreted frizzled-related protein 1 (SFRP1), and provide evidence that high expression of two of these genes correlates with goodprognosis. We were able to demonstrate that both the canonical Wnt3 and the alternative Wnt5A ligands are highly expressed in neuroblastic tumours and cell lines, and specifically activate the DVL3 Wnt co-receptor protein in SJNB8 neuroblastoma cells. These results suggest involvement of MSX1 in Wnt signallingand demonstrate activity of the more upstream Wnt pathway in neuroblastic cells.#CI- Copyright 2009 Elsevier Ireland Ltd. ALL rights reserved.

BACKGROUND: Wilms tumor is the most common pediatric renal malignancy, but the parameters that are important to its invasion capacity are poorly understood. The aim of this study was to identify new proteins associated with the invasion capacity of Wilms tumor. PROCEDURE: Gene expression profiles for 15 primary Wilms tumor samples were determined by Affymetrix Genechip(R) Human Genome Ul33A microarray analysis. The gene expression profiles for selected genes was furtherconfirmed by quantitative RT-PCR analysis. Immunohistochemical analysis was performed on 25 Wilms tumor cases to confirm expression for Bcl2A1, EphB2, MSX1,and RIN1. RESULTS: Using microarray analysis 14 genes showed differential expression (P < 0.05) comparing stage 1 non-invasive Wilms tumor to stages 2-4 invasive Wilms tumor. The differential expression for Bcl2A1, EphB2, MSX1, and RIN1 was confirmed by quantitative RT-PCR. MSX1 protein was statistically significantly lower in stages 2-4 invasive Wilms tumor cases compared to stage 1non-invasive cases (P = 0.013). EphB2 protein was higher in stages 2-4 Wilms tumor cases compared to stage 1 cases (P = 0.006). There was no statistically significant difference between stages 1 and 2-4 Wilms tumor for Bcl2A1 (P = 0.230) or RIN1 (P = 0.969) at the protein level. CONCLUSION: Our results indicate that MSX1 may be associated with the invasion capacity of Wilms tumors. RIN1 is a downstream effector of RAS and Bcl2A1 functions as an anti-apoptotic protein. EphB2 is an ephrin receptor and is up-regulated in invasive tumors but its role needs to be confirmed in further cases of Wilms tumors.#CI- Copyright (c) 2011 Wiley-Liss, Inc.