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oai:docta.ucm.es:20.500.14352/1168982025-01-30T01:11:59Zcom_20.500.14352_14col_20.500.14352_15

Morán, Alberto Iniesta Serrano, María Pilar Juan Chocano, María Del Carmen De Gonzalez-Quevedo, Rosa Sánchez Pernaute, Andrés Díaz-Rubio García, Eduardo Cajal, SRY Torres García, Antonio José Balibrea Cantero, José Luis Benito De Las Heras, Manuel R. 2025-01-29T13:00:12Z 2025-01-29T13:00:12Z 2002-07-01 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 0008-5472 https://hdl.handle.net/20.500.14352/116898 1538-7445 https://pubmed.ncbi.nlm.nih.gov/12097300/ 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. eng http://creativecommons.org/licenses/by/4.0/ restricted access Attribution 4.0 International Stromelysin-1 promoter mutations impair gelatinase B activation in high microsatellite instability sporadic colorectal tumors journal article