Mismatch repair and microsatellite instability in esophageal cancer cells.
Using in vitro mismatch repair (MMR) assay, we have identified 3 of 22 esophageal cancer cell lines exhibiting reduced MMR activity. By means of gel-shift assay, decreased binding ability to GT mismatch and CA loop was observed in these 3 cell lines. However, we could not find any mutations in the hMSH2, hMSH3 and hMSH6 genes, the protein products of which exhibit mismatch binding activity in human cells. In addition, when using antibodies against 5 MMR-related proteins (hMSH2, hMSH3, hMSH6, hPMS2 and hMLH1), no aberrant expression was detected in any of them. When we examined 9 microsatellite loci in endogenous genomic DNA, these 3 esophageal cancer cell lines, deficient in MMR, did not exhibit microsatellite instability. However, when we examined the repetitious sequence on exogenous plasmid DNA which was introduced into these 3 esophageal cancer cells, the results suggested that MMR deficiency in esophageal cancer cells could result in moderate instability of the exogenous sequence.
Central Laboratory and Radiation Biology, Aichi Cancer Center Research Institute, Nagoya, Japan. nuchida@aichi-cc.pref.aichi.jp
N
N
Uchida
H
H
Kumimoto
K
K
Nishizawa
S
S
Tokumasu
H
H
Harada
Y
Y
Shimada
K
K
Ishizaki
D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases; D020137:Base Pair Mismatch; D015153:Blotting, Western; D002352:Carrier Proteins; D004247:DNA / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D018895:Microsatellite Repeats; D000070976:Mismatch Repair Endonuclease PMS2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D000074081:MutS Homolog 3 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009687:Nuclear Proteins; D010957:Plasmids / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D017422:Sequence Analysis, DNA; D019680:Trinucleotide Repeat Expansion; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases; D002352:Carrier Proteins; D004247:DNA; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D000070976:Mismatch Repair Endonuclease PMS2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D000074081:MutS Homolog 3 Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; C078444:MSH3 protein, human; C094934:PMS2 protein, human; C497172:MSH2 protein, human; C421109:multidrug resistance-associated protein 1