RT Journal Article
T1 Differential Wnt pathway gene expression and E-cadherin truncation in sporadic colorectal cancers with and without microsatellite instability
A1 Ortega, Paloma
A1 Morán, Alberto
A1 Juan Chocano, María Del Carmen De
A1 Frías, Cristina
A1 Hernandez, Susana
A1 López Asenjo, Jose Antonio
A1 Sánchez Pernaute, Andrés
A1 Torres García, Antonio José
A1 Iniesta Serrano, María Pilar
A1 Benito De Las Heras, Manuel R.
AB Purpose: Alterations in the Wnt pathway play a major role in colorectal cancer with high (MSI-H) or low microsatellite instability (MSS/MSI-L). However, the differential impact of the Wnt pathway components on these tumors is poorly understood. MMP-3 (stromelysin-1) promoter is a target of the mutator phenotype in sporadic colorectal cancer. Among MMP-3 targets, we investigated E-cadherin integrity status in both groups of tumors. Because beta-catenin is the main effector of the Wnt pathway, we have also investigated the differential cellular status of beta-catenin.Experimental Design: Expression profiles of 114 genes related to the Wnt pathway were analyzed by oligo microarrays in 48 tumors classified by their MSI status. In addition, we analyzed 48 sporadic colorectal cancers for E-cadherin integrity status. We performed investigation of beta-catenin and cyclin D1 by immunohistochemistry using tissue arrays containing 96 tumors.Results: Our data show that a group of genes that negatively regulate Wnt signaling are downregulated in MSS/MSI-L as compared with MSI-H colorectal tumors. E-cadherin truncation was significantly higher in MSS/MSI-L as compared with MSI-H tumors, Moreover, MSI-H tumors showed low or null beta-catenin nuclear presence, whereas the group of tumors classified as MSS or MSI-L displayed a high content of the nuclear beta-catenin location.Conclusions: Our results suggest that the differential expression of genes that negatively regulate the Wnt pathway, as well as the status of E-cadherin and beta-catenin in MSI-H or MSS/MSI-L colorectal tumors, shed some light on the different clinical behavior showed by the two groups.
PB American Association for Cancer Research
SN 1078-0432
YR 2008
FD 2008-02-15
LK https://hdl.handle.net/20.500.14352/130050
UL https://hdl.handle.net/20.500.14352/130050
LA eng
NO Ortega P, Morán A, de Juan C, Frías C, Hernández S, López-Asenjo JA, Sánchez-Pernaute A, Torres A, Iniesta P, Benito M. Differential Wnt pathway gene expression and E-cadherin truncation in sporadic colorectal cancers with and without microsatellite instability. Clin Cancer Res. 2008 Feb 15;14(4):995-1001. doi: 10.1158/1078-0432.CCR-07-1588
DS Docta Complutense
RD 19 ene 2026