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Forty-nine gastric cancer cell lines with integrative genomic profiling for development of c-MET inhibitor

Authors
 Hyun Jeong Kim  ;  Sun Kyoung Kang  ;  Woo Sun Kwon  ;  Tae Soo Kim  ;  Inhye Jeong  ;  Hei-Cheul Jeung  ;  Michael Kragh  ;  Ivan D Horak  ;  Hyun Cheol Chung  ;  Sun Young Rha 
Citation
 International Journal of Cancer, Vol.143(1) : 151-159, 2018 
Journal Title
 International Journal of Cancer 
ISSN
 0020-7136 
Issue Date
2018
Keywords
HGF ; MET ; cell line ; gastric cancer ; targeted therapy
Abstract
Receptor tyrosine kinase MET (c-MET) has received considerable attention as a potential target for gastric cancer (GC) therapy and a number of c-MET inhibitors have been developed. For successful drug development, proper preclinical studies especially using patient derived cancer cell lines are very important. We profiled MET and MET-related characteristics in 49 GC cell lines to utilize them as models in preclinical studies of GC. Forty-nine cell lines were analyzed for genetic, biological, and molecular status to characterize MET and MET-related molecules. Four c-MET inhibitors were tested to elucidate the dependency on MET pathway in the 49 GC cell lines. Six of 49 cell lines were MET amplified with overexpression of c-MET and p-MET. The variants of MET were not associated with c-MET expression or amplification. Hs746T showed an exon 14 deletion in conjunction with MET amplification. The cell lines were divided into 6 MET amplified, 2 c-MET overexpressed, 2 hepatocyte growth factor (HGF) overexpressed, and 39 MET-negative subgroups. Except tivantinib, the c-MET inhibitors showed higher inhibition (%) in MET amplified than in MET nonamplified cell lines that MET amplified cell lines showed MET pathway dependency. However, the c-MET overexpressed and HGF overexpressed cell lines showed moderate dependency on MET pathway. Well-characterized cell lines are very important in studying drug development. Our 49 GC cell lines had various characteristics of MET and MET-related molecules and MET pathway dependency. These provide a promising platform for development of various RTK inhibitors including c-MET inhibitors.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162494
Full Text
https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.31304
DOI
10.1002/ijc.31304
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
김태수(Kim, Tae Soo)
라선영(Rha, Sun Young)
정현철(Chung, Hyun Cheol) ORCID logo https://orcid.org/0000-0002-0920-9471
정희철(Jeung, Hei Cheul)
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