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Mitotic Checkpoint Protein hsMAD2 as a Marker Predicting Liver Metastasis of Human Gastric Cancers

hsMAD2, the human homologue of mitotic arrest deficient 2 (MAD2), is a key component of the mitotic checkpoint system. Recently, mutations and decreased expression of mitotic checkpoint genes including hsMAD2 have been reported in cancer cell lines with defective mitotic checkpoint. However, the gen...

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Autores principales: Tanaka, Kouji, Nishioka, Junji, Kato, Keiko, Nakamura, Akiko, Mouri, Tomomi, Miki, Chikao, Kusunoki, Masato, Nobori, Tsutomu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926839/
https://www.ncbi.nlm.nih.gov/pubmed/11572763
http://dx.doi.org/10.1111/j.1349-7006.2001.tb01186.x
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author Tanaka, Kouji
Nishioka, Junji
Kato, Keiko
Nakamura, Akiko
Mouri, Tomomi
Miki, Chikao
Kusunoki, Masato
Nobori, Tsutomu
author_facet Tanaka, Kouji
Nishioka, Junji
Kato, Keiko
Nakamura, Akiko
Mouri, Tomomi
Miki, Chikao
Kusunoki, Masato
Nobori, Tsutomu
author_sort Tanaka, Kouji
collection PubMed
description hsMAD2, the human homologue of mitotic arrest deficient 2 (MAD2), is a key component of the mitotic checkpoint system. Recently, mutations and decreased expression of mitotic checkpoint genes including hsMAD2 have been reported in cancer cell lines with defective mitotic checkpoint. However, the genetic alterations in the genomic hsMAD2 gene have not been determined in gastric cancers. Moreover, the biological implications of the overexpressed hsMAD2 in primary cancers are unknown. In this study, we analyzed 32 primary gastric cancers with polymerase chain reaction (PCR) amplification of all exons, including flanking intronic sequences, of the genomic hsMAD2 gene followed by direct DNA sequencing. We also measured the hsMAD2 protein levels in cancer and normal tissues by semi‐quantitative immunoblotting. No mutations were found in the coding sequences, although three single nucleotide polymorphisms (SNPs) were identified in the noncoding sequences in 13 of 32 patients. These SNPs were not associated with either hsMAD2 expression or disease progression. The semi‐quantitative western blot analysis showed hsMAD2 was significantly overexpressed in gastric cancer tissues compared with corresponding normal tissues (P<0.001). The calculated ratio of the hsMAD2 protein in cancer tissue (C) to that in corresponding normal tissue (N) (C/N ratio) was significantly higher in patients with well differentiated adenocarcinoma (P=0.0274) or with synchronous liver metastasis (P=0.0025). A C/N ratio greater than 3 was observed more frequently in patients with synchronous liver metastasis. Therefore, C/N ratio >3 may be clinically important as a predictive indicator for metachronous liver metastasis of gastric cancers.
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spelling pubmed-59268392018-05-11 Mitotic Checkpoint Protein hsMAD2 as a Marker Predicting Liver Metastasis of Human Gastric Cancers Tanaka, Kouji Nishioka, Junji Kato, Keiko Nakamura, Akiko Mouri, Tomomi Miki, Chikao Kusunoki, Masato Nobori, Tsutomu Jpn J Cancer Res Article hsMAD2, the human homologue of mitotic arrest deficient 2 (MAD2), is a key component of the mitotic checkpoint system. Recently, mutations and decreased expression of mitotic checkpoint genes including hsMAD2 have been reported in cancer cell lines with defective mitotic checkpoint. However, the genetic alterations in the genomic hsMAD2 gene have not been determined in gastric cancers. Moreover, the biological implications of the overexpressed hsMAD2 in primary cancers are unknown. In this study, we analyzed 32 primary gastric cancers with polymerase chain reaction (PCR) amplification of all exons, including flanking intronic sequences, of the genomic hsMAD2 gene followed by direct DNA sequencing. We also measured the hsMAD2 protein levels in cancer and normal tissues by semi‐quantitative immunoblotting. No mutations were found in the coding sequences, although three single nucleotide polymorphisms (SNPs) were identified in the noncoding sequences in 13 of 32 patients. These SNPs were not associated with either hsMAD2 expression or disease progression. The semi‐quantitative western blot analysis showed hsMAD2 was significantly overexpressed in gastric cancer tissues compared with corresponding normal tissues (P<0.001). The calculated ratio of the hsMAD2 protein in cancer tissue (C) to that in corresponding normal tissue (N) (C/N ratio) was significantly higher in patients with well differentiated adenocarcinoma (P=0.0274) or with synchronous liver metastasis (P=0.0025). A C/N ratio greater than 3 was observed more frequently in patients with synchronous liver metastasis. Therefore, C/N ratio >3 may be clinically important as a predictive indicator for metachronous liver metastasis of gastric cancers. Blackwell Publishing Ltd 2001-09 /pmc/articles/PMC5926839/ /pubmed/11572763 http://dx.doi.org/10.1111/j.1349-7006.2001.tb01186.x Text en
spellingShingle Article
Tanaka, Kouji
Nishioka, Junji
Kato, Keiko
Nakamura, Akiko
Mouri, Tomomi
Miki, Chikao
Kusunoki, Masato
Nobori, Tsutomu
Mitotic Checkpoint Protein hsMAD2 as a Marker Predicting Liver Metastasis of Human Gastric Cancers
title Mitotic Checkpoint Protein hsMAD2 as a Marker Predicting Liver Metastasis of Human Gastric Cancers
title_full Mitotic Checkpoint Protein hsMAD2 as a Marker Predicting Liver Metastasis of Human Gastric Cancers
title_fullStr Mitotic Checkpoint Protein hsMAD2 as a Marker Predicting Liver Metastasis of Human Gastric Cancers
title_full_unstemmed Mitotic Checkpoint Protein hsMAD2 as a Marker Predicting Liver Metastasis of Human Gastric Cancers
title_short Mitotic Checkpoint Protein hsMAD2 as a Marker Predicting Liver Metastasis of Human Gastric Cancers
title_sort mitotic checkpoint protein hsmad2 as a marker predicting liver metastasis of human gastric cancers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926839/
https://www.ncbi.nlm.nih.gov/pubmed/11572763
http://dx.doi.org/10.1111/j.1349-7006.2001.tb01186.x
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