RT Journal Article
T1 Stromelysin-1 promoter mutations impair gelatinase B activation in high microsatellite instability sporadic colorectal tumors
A1 Morán, Alberto
A1 Iniesta Serrano, María Pilar
A1 Juan Chocano, María Del Carmen De
A1 Gonzalez-Quevedo, Rosa
A1 Sánchez Pernaute, Andrés
A1 Díaz-Rubio García, Eduardo
A1 Cajal, SRY
A1 Torres García, Antonio José
A1 Balibrea Cantero, José Luis
A1 Benito De Las Heras, Manuel R.
AB Colorectal cancers from the mutator phenotype pathway display distinctive pathological features and confer a lesser aggressiveness than colorectal adenocarcinomas originated by the suppressor pathway. The goal of this work was to test whether tumors developed through the mutator pathway could show a decrease in matrix metalloproteinase (MMP) activity. We evaluated levels and activity of gelatinase A (MMP-2) and gelatinase B (MMP-9), as well as stromelysin-1 (MMP-3) expression in 101 sporadic colorectal tumors in consideration of the microsatellite instability (MSI) status of the groups. Gelatinases were analyzed by ELISA and zymography. The MMP-3 study was performed by real-time quantitative PCR. MMP-9 total levels were significantly higher in MSI-H tumors. However, levels of the active MMP-9 form were significantly much lower in this group of tumors. Data from real-time quantitative PCR indicated that levels of MMP-3 for MSI-L/MSS tumors were much higher as compared with those observed in MSI-H cancers (P = 0.033). Moreover, all MSI-H tumors showed nucleotide insertions and/or deletions in MMP-3 promoter. These mutations were not observed in the group of MSI-L/MSS tumors. Our data indicate that the MMP-3 promoter constitutes a novel target of the defective mismatch repair machinery in sporadic colorectal tumors, resulting in a dramatic decrease in the levels of the active MMP-9 form, which may result in a lessened capacity for invasion.
SN 0008-5472
YR 2002
FD 2002-07-01
LK https://hdl.handle.net/20.500.14352/116898
UL https://hdl.handle.net/20.500.14352/116898
LA eng
NO Morán A, Iniesta P, de Juan C, González-Quevedo R, Sánchez-Pernaute A, Díaz- Rubio E, Ramón y Cajal S, Torres A, Balibrea JL, Benito M. Stromelysin-1 promoter mutations impair gelatinase B activation in high microsatellite instability spo
DS Docta Complutense
RD 18 dic 2025