Stimulation of mammary tumorigenesis by systemic tissue inhibitor of matrix metalloproteinase 4 gene delivery.
Cancer Res
; 61(6): 2365-70, 2001 Mar 15.
Article
en En
| MEDLINE
| ID: mdl-11289097
ABSTRACT
Tissue inhibitors of matrix metalloproteinase (TIMPs) are multifunctional proteins with both matrix metalloproteinase (MMP) inhibitory effects and growth-regulatory activity. TIMPs inhibit MMP activity, suggesting a use for cancer gene therapy. However, here we report that systemic administration of human TIMP-4 by electroporation-mediated i.m. injection of naked TIMP-4 DNA stimulates tumorigenesis of human breast cancer cells in nude mice. Consistent with tumor stimulation, TIMP-4 up-regulates Bcl-2 and Bcl-X(L) protein. TIMP-4 also inhibits apoptosis in human breast cancer cells in vitro and mammary tumors in vivo. A synthetic MMP inhibitor BB-94 did not have such antiapoptotic effect. Analysis of TIMP-4 expression in human mammary specimens indicates that TIMP-4 protein is increased in mammary carcinoma cells compared with normal mammary epithelial cells. These data indicate an antiapoptotic activity in breast cancer cells and a tumor-stimulating effect of TIMP-4 when administrated systemically.
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Banco de datos:
MEDLINE
Asunto principal:
Mama
/
Neoplasias de la Mama
/
ADN
/
Transformación Celular Neoplásica
/
Inhibidores Tisulares de Metaloproteinasas
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cancer Res
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos