Frequent hypermethylation of CpG islands and loss of expression of the 14-3-3 σ gene in human hepatocellular carcinoma View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2000-11-02

AUTHORS

Norikazu Iwata, Hiroyuki Yamamoto, Shigeru Sasaki, Fumio Itoh, Hiromu Suzuki, Takefumi Kikuchi, Hiroyuki Kaneto, Shouhei Iku, Itaru Ozeki, Yoshiyasu Karino, Toshihiro Satoh, Joji Toyota, Masaaki Satoh, Takao Endo, Kohzoh Imai

ABSTRACT

The 14-3-3 σ gene has been implicated in G2/M cell cycle arrest by p53. Frequent inactivation of the 14-3-3 σ gene by hypermethylation of CpG islands has recently been reported in human breast carcinoma. The aim of this study was to examine the methylation status of CpG islands of the 14-3-3 σ gene in hepatocellular carcinoma (HCC). The methylation status of the 14-3-3 σ gene was evaluated in four normal liver tissues and 19 paired specimens of carcinoma and adjacent non-tumorous liver tissues using bisulfite-single strand conformation polymorphism (bisulfite-SSCP), a combination of sodium bisulfite modification and fluorescence-based polymerase chain reaction (PCR)-SSCP. The 14-3-3 σ protein expression was examined by immunohistochemical staining. Hypermethylation of CpG islands of the 14-3-3 σ gene was detected in 89% (17/19) of the HCC tissues but not in any of the four normal liver tissues. All of the 14 methylation-positive HCC samples analysed by immunohistochemistry showed loss of 14-3-3 σ expression, while both of the methylation-negative HCC samples retained the expression, and a significant correlation was found between methylation and loss of expression. Lower levels of methylation were detected in adjacent non-tumorous liver tissues (6/16 in cirrhotic tissues and 1/3 in chronic hepatitis tissues), but the 14-3-3 σ expression was retained in all of these tissues. In a methylation-positive HCC cell line, HLE, 5-aza-2′-deoxycytidine (5-aza-dC)-induced demethylation of CpG islands led to reactivation of gene expression, indicating that hypermethylation plays a causal role in inactivation of the 14-3-3 σ gene in HCC. Hypermethylation and the resulting loss of expression of the 14-3-3 σ gene corresponds to one of the most common abnormalities reported to date in HCC, suggesting their crucial role in the development and/or progression of HCC. More... »

PAGES

5298-5302

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1203898

DOI

http://dx.doi.org/10.1038/sj.onc.1203898

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1029696632

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11077447


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28 schema:description The 14-3-3 σ gene has been implicated in G2/M cell cycle arrest by p53. Frequent inactivation of the 14-3-3 σ gene by hypermethylation of CpG islands has recently been reported in human breast carcinoma. The aim of this study was to examine the methylation status of CpG islands of the 14-3-3 σ gene in hepatocellular carcinoma (HCC). The methylation status of the 14-3-3 σ gene was evaluated in four normal liver tissues and 19 paired specimens of carcinoma and adjacent non-tumorous liver tissues using bisulfite-single strand conformation polymorphism (bisulfite-SSCP), a combination of sodium bisulfite modification and fluorescence-based polymerase chain reaction (PCR)-SSCP. The 14-3-3 σ protein expression was examined by immunohistochemical staining. Hypermethylation of CpG islands of the 14-3-3 σ gene was detected in 89% (17/19) of the HCC tissues but not in any of the four normal liver tissues. All of the 14 methylation-positive HCC samples analysed by immunohistochemistry showed loss of 14-3-3 σ expression, while both of the methylation-negative HCC samples retained the expression, and a significant correlation was found between methylation and loss of expression. Lower levels of methylation were detected in adjacent non-tumorous liver tissues (6/16 in cirrhotic tissues and 1/3 in chronic hepatitis tissues), but the 14-3-3 σ expression was retained in all of these tissues. In a methylation-positive HCC cell line, HLE, 5-aza-2′-deoxycytidine (5-aza-dC)-induced demethylation of CpG islands led to reactivation of gene expression, indicating that hypermethylation plays a causal role in inactivation of the 14-3-3 σ gene in HCC. Hypermethylation and the resulting loss of expression of the 14-3-3 σ gene corresponds to one of the most common abnormalities reported to date in HCC, suggesting their crucial role in the development and/or progression of HCC.
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35 G2/M cell cycle arrest
36 HCC cell lines
37 HCC samples
38 HCC tissues
39 HLE
40 M cell cycle arrest
41 SSCP
42 abnormalities
43 adjacent non-tumorous liver tissues
44 aim
45 arrest
46 breast carcinoma
47 carcinoma
48 causal role
49 cell cycle arrest
50 cell lines
51 chain reaction
52 combination
53 combination of sodium
54 common abnormality
55 conformation polymorphism
56 correlation
57 crucial role
58 cycle arrest
59 date
60 demethylation
61 development
62 expression
63 fluorescence-based polymerase chain reaction
64 frequent hypermethylation
65 frequent inactivation
66 gene expression
67 genes
68 hepatocellular carcinoma
69 human breast carcinoma
70 human hepatocellular carcinoma
71 hypermethylation
72 immunohistochemical staining
73 immunohistochemistry
74 inactivation
75 islands
76 levels
77 lines
78 liver tissue
79 loss
80 loss of expression
81 low levels
82 methylation
83 methylation status
84 modification
85 non-tumorous liver tissues
86 normal liver tissue
87 p53
88 polymerase chain reaction
89 polymorphism
90 progression
91 progression of HCC
92 protein expression
93 reaction
94 reactivation
95 role
96 samples
97 significant correlation
98 sodium
99 specimens
100 specimens of carcinoma
101 staining
102 status
103 strand conformation polymorphism
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