Source:http://linkedlifedata.com/resource/pubmed/id/17786318
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2007-9-5
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| pubmed:abstractText |
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a 465-kDa catalytic subunit of DNA-PK, a DNA repair apparatus. DNA-PKcs has been reported to be a tumor suppressor, but details of its expression in human cancer are controversial. To determine the protein expression and clinical implications of DNA-PKcs in gastric carcinogenesis and cancer progression, we evaluated its expression status by immunohistochemistry in 122 non-neoplastic gastric mucosa samples, and in 115 gastric adenomas and 564 consecutive gastric cancers. In addition, we evaluated the clinicopathologic characteristics of gastric cancers showing altered DNA-PKcs expression, and performed microsatellite instability (MSI) analysis at BAT-26 and frameshift mutation analysis of DNA-PKcs. DNA-PKcs expression was negative in foveolar epithelium of normal gastric mucosal tissues, but was positive in most Helicobacter pylori-associated gastritis, intestinal metaplasia and gastric adenoma tissues. In gastric cancers, negative expression of DNA-PKcs was found in 114 of the 564 (20.2%) cancers and was significantly associated with intratumoral neutrophils, MSI-high (H) phenotype, tumor progression, and poor patient survival (p<0.05). Frameshift mutations of (A)10 mononucleotide repeats in DNA-PKcs were found in 24.3% of MSI-H gastric cancers and these were associated with negative expression of DNA-PKcs. Although patients with MSI-H gastric cancers were found to have a lower risk of lymph node metastasis, gastric cancers harboring the (A)10 mutation of DNA-PKcs were found to have a higher risk of lymph node metastasis. In conclusion, the expression of DNA-PKcs was found to be altered during gastric carcinogenesis and negative DNA-PKcs expression was associated with gastric cancer progression. The (A)10 frameshift mutation of DNA-PKcs in gastric cancers was a target of defective mismatch repair, and was associated with lymph node metastasis.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
1019-6439
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
31
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
859-66
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:17786318-Adenocarcinoma,
pubmed-meshheading:17786318-Adenocarcinoma, Mucinous,
pubmed-meshheading:17786318-Adenoma,
pubmed-meshheading:17786318-DNA Mismatch Repair,
pubmed-meshheading:17786318-DNA-Activated Protein Kinase,
pubmed-meshheading:17786318-Female,
pubmed-meshheading:17786318-Frameshift Mutation,
pubmed-meshheading:17786318-Gastric Mucosa,
pubmed-meshheading:17786318-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:17786318-Helicobacter Infections,
pubmed-meshheading:17786318-Helicobacter pylori,
pubmed-meshheading:17786318-Humans,
pubmed-meshheading:17786318-Intestinal Neoplasms,
pubmed-meshheading:17786318-Lymphatic Metastasis,
pubmed-meshheading:17786318-Male,
pubmed-meshheading:17786318-Metaplasia,
pubmed-meshheading:17786318-Microsatellite Instability,
pubmed-meshheading:17786318-Middle Aged,
pubmed-meshheading:17786318-Neoplasm Invasiveness,
pubmed-meshheading:17786318-Stomach Neoplasms
|
| pubmed:year |
2007
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| pubmed:articleTitle |
Altered expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) during gastric carcinogenesis and its clinical implications on gastric cancer.
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| pubmed:affiliation |
Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi 463-707, Korea.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|