Browse

Activation of notch signaling in a xenograft model of brain metastasis

Cited 53 time in Web of Science Cited 53 time in Scopus
Authors
Nam, Do-Hyun; Jeon, Hye-Min; Kim, Shiyeon; Kim, Mi Hyun; Lee, Young-Ju; Lee, Min Su; Kim, Hyunggee; Joo, Kyeung Min; Lee, Dong-Sup; Price, Janet E; Bang, Sa Ik; Park, Woong-Yang
Issue Date
2008-07-03
Publisher
American Association for Cancer Research
Citation
Clin Cancer Res. 2008;14(13): 4059-66
Keywords
AnimalsBrain/metabolism/*pathologyBrain Neoplasms/pathologyCell Line, TumorCell Movement*Gene Expression Profiling*Gene Expression Regulation, NeoplasticHumansMiceModels, BiologicalNeoplasm InvasivenessNeoplasm MetastasisNeoplasm TransplantationProtein Structure, TertiaryReceptors, Notch/*metabolism
Abstract
PURPOSE: The potential of metastasis can be predicted from clinical features like tumor size, histologic grade, and gene expression patterns. We examined the whole-genome transcriptomic profile of a xenograft model of breast cancer to understand the characteristics of brain metastasis. EXPERIMENTAL DESIGN: Variants of the MDA-MB-435 cell were established from experimental brain metastases. The LvBr2 variant was isolated from lesions in a mouse injected in the left ventricle of the heart, and these cells were used for two cycles of injection into the internal carotid artery and selection of brain lesions, resulting in the Br4 variant. To characterize the different metastatic variants, we examined the gene expression profile of MDA-MB-435, LvBr2, and Br4 cells using microarrays. RESULTS: We could identify 2,016 differentially expressed genes in Br4 by using the F test. Various metastasis-related genes and a number of genes related to angiogenesis, migration, tumorigenesis, and cell cycle were differentially expressed by the Br4 cells. Notably, the Notch signaling pathway was activated in Br4, with increased Jag2 mRNA, activated Notch intracellular domain, and Notch intracellular domain/CLS promoter-luciferase activity. Br4 cells were more migratory and invasive than MDA-MB-435 cells in collagen and Matrigel Transwell assays, and the migration and invasion of Br4 cells were significantly inhibited by inactivation of Notch signaling using DAPT, a gamma-secretase inhibitor, and RNA interference-mediated knockdown of Jagged 2 and Notch1. CONCLUSIONS: Taken together, these results suggest that we have isolated variants of a human cancer cell line with enhanced brain metastatic properties, and the activation of Notch signaling might play a crucial role in brain metastasis.
ISSN
1078-0432 (Print)
Language
English
URI
http://clincancerres.aacrjournals.org/content/14/13/4059.full.pdf

http://hdl.handle.net/10371/67496
DOI
https://doi.org/10.1158/1078-0432.CCR-07-4039
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biochemistry & Molecular Biology (생화학교실)Journal Papers (저널논문_생화학교실)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse