Augmented membrane type 1 matrix metalloproteinase (MT1-MMP):MMP-2 messenger RNA ratio in gastric carcinomas with poor prognosis.
Clin Cancer Res
; 4(9): 2179-86, 1998 Sep.
Article
em En
| MEDLINE
| ID: mdl-9748137
ABSTRACT
The activation of zymogen and the amount of proteinase and its inhibition are important in determining the eventual activity of matrix-degrading enzymes involved in tumor aggressiveness. To evaluate a gene complement leading to matrix metalloproteinase 2 (MMP-2; Mr 72,000 gelatinase) activity, membrane type 1 MMP (MT1-MMP), urokinase-type plasminogen activator, MMP-2, and tissue inhibitor of metalloproteinase 2 transcriptional levels were measured in gastric carcinoma biopsies. Comparative tumornormal tissue reverse transcription-PCR in a cohort of 25 patients revealed up to a 10-fold difference in the expression of MT1-MMP, a metalloproteinase that has been proposed as a membrane receptor activator of MMP-2; a 1-unit increment resulted in a 30% risk to survival. A 20% risk also resulted from a 1-unit increment in the MT1-MMP MMP-2 ratio, which showed differences of up to 15-fold. Instead, the expression of urokinase-type plasminogen activator, which trips off a cascade ending in the activation of MMP-2, as well as the expression of MMP-2 itself and its inhibitor, tissue inhibitor of metalloproteinase 2, lacked correlation with patient follow-up. Zymography revealed MMP-2 activities that were often in conflict with the transcription results and also with follow-up. The results suggest the evaluation of MT1-MMP and/or MT1-MMPMMP-2 transcription as a new preoperative molecular-level prognostic factor for gastric carcinoma.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
/
Metaloendopeptidases
/
Gelatinases
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article