RRC ID |
38456
|
著者 |
Nakamura J, Kitajima Y, Kai K, Hashiguchi K, Hiraki M, Noshiro H, Miyazaki K.
|
タイトル |
Expression of hypoxic marker CA IX is regulated by site-specific DNA methylation and is associated with the histology of gastric cancer.
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ジャーナル |
Am J Pathol
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Abstract |
The hypoxic marker carbonic anhydrase (CA) IX has been recognized as a tumor-associated protein and is essential for cancer development. However, because CA IX expression does not always correlate with hypoxia, its regulatory mechanism remains unclear. The objective of the present study was to clarify the role and regulation of CA IX expression in gastric cancer. The immunohistochemical expression of CA IX and hypoxia-inducible factor-1α was assessed in 77 patients with gastric cancer. A methylation-sensitive restriction enzyme method was used to quantify site-specific methylation at -74 bp in the CA9 promoter in tissue from patients with gastric cancer and in corresponding normal tissue. CA9 expression in cell lines was strongly dependent on methylation status but not hypoxic stimuli. In tissue from patients with gastric cancer, the quantity of methylation was significantly correlated with the protein expression (P = 0.003). Moreover, the methylation value was significantly lower in intestinal-type compared with diffuse-type cancer (P = 0.003). Compared with normal mucosa, intestinal-type cancer demonstrated significant hypomethylation, whereas diffuse-type cancer exhibited hypermethylation. In conclusion, expression of CA IX in gastric cancer is predominantly regulated by methylation of a single CpG rather than by hypoxia. Furthermore, epigenetic alterations in CA9 differ between the intestinal and diffuse types of gastric cancer.
|
巻・号 |
178(2)
|
ページ |
515-24
|
公開日 |
2011-2-1
|
DOI |
10.1016/j.ajpath.2010.10.010
|
PII |
S0002-9440(10)00103-3
|
PMID |
21281785
|
PMC |
PMC3069889
|
MeSH |
Adult
Aged
Aged, 80 and over
Antigens, Neoplasm / genetics*
Antigens, Neoplasm / metabolism
Azacitidine / pharmacology
Azacitidine / therapeutic use
Carbonic Anhydrase IX
Carbonic Anhydrases / genetics*
Carbonic Anhydrases / metabolism
Cell Hypoxia / drug effects
Cell Hypoxia / genetics
Cell Line, Tumor
DNA Methylation / drug effects
DNA Methylation / genetics*
Female
Gene Expression Regulation, Neoplastic* / drug effects
Humans
Hydroxamic Acids / pharmacology
Hydroxamic Acids / therapeutic use
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Immunohistochemistry
Kaplan-Meier Estimate
Male
Middle Aged
Promoter Regions, Genetic / genetics
Stomach Neoplasms / drug therapy
Stomach Neoplasms / enzymology
Stomach Neoplasms / genetics*
Stomach Neoplasms / pathology*
|
IF |
3.491
|
引用数 |
26
|
WOS 分野
|
PATHOLOGY
|
リソース情報 |
ヒト・動物細胞 |
|