title: Retroviral delivery of TIMP-2 inhibits H-ras-induced migration and invasion in MCF10A human breast epithelial cells.
abstract: The matrix metalloproteases (MMPs) play important roles in invasion, metastasis and angiogenesis in various cell types. Tissue inhibitor of metalloprotease (TIMP)-2, an endogenous inhibitor of MMP-2, has been shown to inhibit invasion and metastasis. We have previously shown that MMP-2 is responsible for the H-ras-induced invasive and migrative phenotypes in MCF10A human breast epithelial cells. Here, we investigated the effect of TIMP-2 overexpression on migration and invasion in H-ras MCF10A cells. Human TIMP-2 gene was effectively introduced into H-ras MCF10A cells by retrovirus-mediated gene delivery. TIMP-2 overexpression mediated by retrovirus significantly inhibited migration as well as invasion of H-ras MCF10A cells in a dose-dependent manner. We also show the antiangiogenic effect of TIMP-2 gene delivery. Taken together, our study shows that retrovirus-mediated delivery of TIMP-2 efficiently inhibits metastatic progression of ras-transformed human breast epithelial cells, suggesting a potential use of the TIMP-2 gene therapy for the treatment of breast cancer.
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul 132-714, South Korea.
authors.forename: Seong-Min
authors.initials: SM
authors.lastname: Ahn
authors.forename: Seo-Jin
authors.initials: SJ
authors.lastname: Jeong
authors.forename: Yeon-Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Yeowon
authors.initials: Y
authors.lastname: Sohn
authors.forename: Aree
authors.initials: A
authors.lastname: Moon
mesh_terms: D002460:Cell Line; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002465:Cell Movement; D002478:Cells, Cultured; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D015151:Immunoblotting; D008957:Models, Genetic; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000628:therapy*; D009389:Neovascularization, Pathologic; D010641:Phenotype; D012190:Retroviridae / Q000235:genetics*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*; D014945:Wound Healing; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D013778:Tetrazolium Salts; D013844:Thiazoles; D019716:Tissue Inhibitor of Metalloproteinase-2; D018631:ras Proteins; C022616:thiazolyl blue