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Cited by 29Genetic factors in colorectal cancerDNA Repair MechanismsEpigenetics and DNA Methylation

Alterations of DNA mismatch repair proteins and microsatellite instability levels in gastric cancer cell lines

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Yao, Yuan, Tao, Hong, Kim, Jae J, Burkhead, Benjamin, Carloni, Emilia, Gasbarrini, Antonio, Sepulveda, Antonia R·2004·Laboratory Investigation
DOI 10.1038/labinvest.3700117
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Abstract

Alterations in DNA mismatch repair (MMR) proteins result in microsatellite instability (MSI), increased mutation accumulation at target genes and cancer development. About one-third of gastric cancers display high-level microsatellite instability (MSI-High) and low-level microsatellite instability (MSI-Low) is frequently detected. To determine whether variations in the levels of MMR proteins or mutations in the main DNA MMR genes are associated with MSI-Low and MSI-High in gastric cancer cell lines, the MSI status (MSI-High, MSI-Low or MS-Stable (MSS)) of 14 gastric cancer lines was determined using multiple clone analysis with a panel of five microsatellite markers. Protein levels of hMLH1, hMSH2, hMSH6, hPMS2 and hPMS1 were determined by Western blot. Sequence analysis of hMLH1 and hMSH2 was performed and the methylation status of the hMLH1 promoter was examined. The cell lines SNU1 and SNU638 showed MSI-High, decreased to essentially absent hMLH1 and hPMS2 and reduced hPMS1 and hMSH6 protein levels. The hMLH1 promoter region was hypermethylated in SNU638 cells. The MKN28, MKN87, KATOIII and SNU601 cell lines showed MSI-Low. The MMR protein levels of cells with MSI-Low status was similar to the levels detected in MSS cells. A marked decrease in the expression levels of MutL MMR proteins (hMLH1, hPMS2 and hPMS1) is associated with high levels of MSI mutations in gastric cancer cells. Gastric cancer cell lines with MSI-Low status do not show significant changes in the levels of the main DNA MMR proteins or mutations in the DNA mismatch repair genes hMSH2 and hMLH1. These well-characterized gastric cancer cell lines are a valuable resource to further our understanding of DNA MMR deficiency in cancer development, progression and prognosis.

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Cited by

Sorted by citations

Authors
Yao, Y., Tao, H., Kim, J. J., Burkhead, B., Carloni, E., Gasbarrini, A., & Sepulveda, A. R.
Affiliations
  • University of Pittsburgh Medical Center (US)
  • University of Pittsburgh (US)
  • Samsung Medical Center (KR)
  • Università Cattolica del Sacro Cuore (IT)
Corresponding author
Sepulveda, Antonia R
ORCID
Venue
Laboratory Investigation
Publisher
Elsevier BV
Published
2004-07
Volume
84
Issue
7
Pages
915-922
ISSN
0023-6837 (ISSN-L)
DOI
10.1038/labinvest.3700117
OpenAlex
W1987706726
Cited by
29
References
0
Citations by year
2025: 3 · 2024: 1 · 2022: 2 · 2020: 3 · 2018: 4 · 2017: 2 · 2016: 1 · 2012: 2
FWCI
1.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Laboratory Investigation (publishedVersion)
  • PubMed (publishedVersion)
Funders
American Cancer Society
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
DNA mismatch repair, microsatellite instability, gastric cancer cell lines, MLH1, MSH2, MSH6, hPMS2, hPMS1, promoter hypermethylation, microsatellite instability-high, mismatch repair deficiency
MeSH terms
MutL Protein Homolog 1, Carrier Proteins, DNA Repair, DNA-Binding Proteins, Humans, Mutation, Neoplasm Proteins, Nuclear Proteins, Promoter Regions, Genetic, Proto-Oncogene Proteins, Stomach Neoplasms, Microsatellite Repeats, DNA Methylation, Base Pair Mismatch, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, MutS Homolog 2 Protein

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