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Immunity to growth factor receptor-bound protein 10, a signal transduction molecule, inhibits the growth of breast cancer in mice

Authors
O-Sullivan, InSugChopra, AmlaCarr, JanaiKim, Tae SungCohen, Edward P.
Issue Date
1-4월-2008
Publisher
AMER ASSOC CANCER RESEARCH
Citation
CANCER RESEARCH, v.68, no.7, pp.2463 - 2470
Indexed
SCIE
SCOPUS
Journal Title
CANCER RESEARCH
Volume
68
Number
7
Start Page
2463
End Page
2470
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/123756
DOI
10.1158/0008-5472.CAN-07-5685
ISSN
0008-5472
Abstract
This study describes the application of a unique strategy to identify breast cancer antigens [tumor-associated antigen (TAA)]. In a mouse model, the strategy led to the identification of growth factor receptor-bound protein 10 (Grb10) as a newly identified TAA. Grb10 is a signal transduction molecule associated with multiple transmembrane tyrosine kinase receptors. It was discovered by comparing microarrays of cellular breast cancer vaccines highly enriched for cells that induced breast cancer immunity in tumor-bearing mice with nonenriched vaccines. The vaccines were prepared by transferring a cDNA expression library derived from SB5b cells, a breast cancer cell line C3H/He origin (H-2(k)), into LM mouse fibroblasts (H-2(k)). As the transferred cDNA integrates spontaneously into the genome of the recipient cells, replicates as the cells divide, and is expressed, the vaccine could be prepared from microgram amounts of tumor tissue. Relatively few cells in the transduced cell population, however, incorporated cDNA fragments that included genes specifying TAA. (The vast majority specified normal cellular constituents.) A unique strategy was used, therefore, to enrich the vaccine for immunotherapeutic cells. Twenty genes were overrepresented in the enriched vaccines. One, the gene for Grb10, was similar to 100-fold overrepresented. To determine if Grb10 in the enriched vaccine was partly responsible for its therapeutic benefits, the gene was transferred into the fibroblast cell line, which was then used as a vaccine. Mice with established breast cancer treated solely by immunization with the modified fibroblasts developed robust immunity to the breast cancer cells, which, in some instances, was sufficient to result in tumor rejection.
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