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Fibulin 1 is downregulated through promoter hypermethylation in gastric cancer.

Cheng YY, Jin H, Liu X, Siu JM, Wong YP, Ng EK, Yu J, Leung WK, Sung JJ, Chan FK - Br. J. Cancer (2008)

Bottom Line: Tumour suppressor genes (TSGs) were frequently inactivated through promoter hypermethylation in gastric carcinoma as well as pre-malignant gastric lesions, suggesting that promoter hypermethylation can be used as a marker to define novel TSGs and also biomarkers for early detection of gastric cancer.FBLN1 expression was downregulated in all of gastric cancer cell lines used (100%, 7 out of 7) and the primary gastric carcinoma tissues (84%, 86 out of 102) and significantly restored after pharmacological demethylation.Ectopic expression of FBLN1 led to the growth inhibition of gastric cancer cells through the induction of apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease, Faculty of Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.

ABSTRACT
Tumour suppressor genes (TSGs) were frequently inactivated through promoter hypermethylation in gastric carcinoma as well as pre-malignant gastric lesions, suggesting that promoter hypermethylation can be used as a marker to define novel TSGs and also biomarkers for early detection of gastric cancer. In an effort to search for such genes aberrantly methylated in gastric cancer development, fibulin 1 (FBLN1) was found as a candidate TSG epigenetically downregulated in gastric cancer. FBLN1 expression was downregulated in all of gastric cancer cell lines used (100%, 7 out of 7) and the primary gastric carcinoma tissues (84%, 86 out of 102) and significantly restored after pharmacological demethylation. Hypermethylation of the FBLN1 promoter was frequently (71%, 5 out of 7) detected in gastric cancer cell lines and primary gastric carcinoma tissues. Ectopic expression of FBLN1 led to the growth inhibition of gastric cancer cells through the induction of apoptosis. In summary, FBLN1 was identified as a novel candidate TSG epigenetically downregulated in gastric cancer.

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FBLN1 promoter is hypermethylated in gastric cancer cell lines. (A) Fibulin 1 has a typical CpG island around exon 1. CpG island was plotted by the GeneTool program. The position of MSP primers is indicated by arrows. (B) The methylation status of the FBLN1 promoter was determined by MSP. M: methylation; U: unmethylation.
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fig2: FBLN1 promoter is hypermethylated in gastric cancer cell lines. (A) Fibulin 1 has a typical CpG island around exon 1. CpG island was plotted by the GeneTool program. The position of MSP primers is indicated by arrows. (B) The methylation status of the FBLN1 promoter was determined by MSP. M: methylation; U: unmethylation.

Mentions: A typical CpG island (CGI) was found around FBLN1 exon 1 using the following criteria: GC content >55%, ObsCpG/ExpCpG >0.65 and length >500 bp (Figure 2A). The methylation status of this CGI in gastric cancer cells was determined by MSP. As shown in Figure 2B, full methylation was detected in five gastric cancer cell lines, whereas the other two cell lines showed partial or no methylation of FBLN1 CGI.


Fibulin 1 is downregulated through promoter hypermethylation in gastric cancer.

Cheng YY, Jin H, Liu X, Siu JM, Wong YP, Ng EK, Yu J, Leung WK, Sung JJ, Chan FK - Br. J. Cancer (2008)

FBLN1 promoter is hypermethylated in gastric cancer cell lines. (A) Fibulin 1 has a typical CpG island around exon 1. CpG island was plotted by the GeneTool program. The position of MSP primers is indicated by arrows. (B) The methylation status of the FBLN1 promoter was determined by MSP. M: methylation; U: unmethylation.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2607230&req=5

fig2: FBLN1 promoter is hypermethylated in gastric cancer cell lines. (A) Fibulin 1 has a typical CpG island around exon 1. CpG island was plotted by the GeneTool program. The position of MSP primers is indicated by arrows. (B) The methylation status of the FBLN1 promoter was determined by MSP. M: methylation; U: unmethylation.
Mentions: A typical CpG island (CGI) was found around FBLN1 exon 1 using the following criteria: GC content >55%, ObsCpG/ExpCpG >0.65 and length >500 bp (Figure 2A). The methylation status of this CGI in gastric cancer cells was determined by MSP. As shown in Figure 2B, full methylation was detected in five gastric cancer cell lines, whereas the other two cell lines showed partial or no methylation of FBLN1 CGI.

Bottom Line: Tumour suppressor genes (TSGs) were frequently inactivated through promoter hypermethylation in gastric carcinoma as well as pre-malignant gastric lesions, suggesting that promoter hypermethylation can be used as a marker to define novel TSGs and also biomarkers for early detection of gastric cancer.FBLN1 expression was downregulated in all of gastric cancer cell lines used (100%, 7 out of 7) and the primary gastric carcinoma tissues (84%, 86 out of 102) and significantly restored after pharmacological demethylation.Ectopic expression of FBLN1 led to the growth inhibition of gastric cancer cells through the induction of apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease, Faculty of Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.

ABSTRACT
Tumour suppressor genes (TSGs) were frequently inactivated through promoter hypermethylation in gastric carcinoma as well as pre-malignant gastric lesions, suggesting that promoter hypermethylation can be used as a marker to define novel TSGs and also biomarkers for early detection of gastric cancer. In an effort to search for such genes aberrantly methylated in gastric cancer development, fibulin 1 (FBLN1) was found as a candidate TSG epigenetically downregulated in gastric cancer. FBLN1 expression was downregulated in all of gastric cancer cell lines used (100%, 7 out of 7) and the primary gastric carcinoma tissues (84%, 86 out of 102) and significantly restored after pharmacological demethylation. Hypermethylation of the FBLN1 promoter was frequently (71%, 5 out of 7) detected in gastric cancer cell lines and primary gastric carcinoma tissues. Ectopic expression of FBLN1 led to the growth inhibition of gastric cancer cells through the induction of apoptosis. In summary, FBLN1 was identified as a novel candidate TSG epigenetically downregulated in gastric cancer.

Show MeSH
Related in: MedlinePlus