Regulation of the Mr 72,000 type IV collagenase by the type I insulin-like growth factor receptor.
Cancer Res
; 58(15): 3243-7, 1998 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-9699649
The Mr 72,000 type IV collagenase [matrix metalloproteinase 2 (MMP-2)] is known to play a central role in the process of invasion and metastasis, but its regulation is not clearly understood. We investigated the role of the type I insulin-like growth factor (IGF-I) in the regulation of tumor cell invasion and the synthesis of MMP-2. Highly invasive murine Lewis lung carcinoma subline H-59 cells, in which expression of the IGF-I receptor (IGF-IR) was blocked by antisense mRNA, had a significantly reduced invasion in reconstituted basement membrane (Matrigel) as compared with that of controls. These cells had a decrease of up to 6-fold in the level of MMP-2 mRNA transcripts, as assessed by reverse transcription-PCR, and a corresponding reduction in protein synthesis, as assessed by the Western blot assay and gelatin zymography. Conversely, overexpression of IGF-IR in a second, poorly invasive carcinoma subline (M-27) with low endogenous levels of the receptor increased MMP-2 mRNA and protein expression by up to 7.5- and 4-fold, respectively. Ligand-mediated activation of the IGF-IR induced MMP-2 synthesis in both cell types. The results identify IGF-I as a regulator of MMP-2 expression and cellular invasion.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Metaloendopeptidasas
/
Receptor IGF Tipo 1
/
Gelatinasas
/
Carcinoma Pulmonar de Lewis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Res
Año:
1998
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Estados Unidos