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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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Fibulin 1 is downregulated and hypermethylated in primary gastric carcinoma tissues. (A) The expression of FBLN1 in gastric carcinoma and adjacent non-tumour tissues was determined by quantitative real-time RT–PCR as in Figure 1A. (B) The methylation status of the FBLN1 promoter in primary gastric carcinoma and adjacent non-tumour tissues was determined by MSP as in Figure 2B. Representative results are shown.
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fig3: Fibulin 1 is downregulated and hypermethylated in primary gastric carcinoma tissues. (A) The expression of FBLN1 in gastric carcinoma and adjacent non-tumour tissues was determined by quantitative real-time RT–PCR as in Figure 1A. (B) The methylation status of the FBLN1 promoter in primary gastric carcinoma and adjacent non-tumour tissues was determined by MSP as in Figure 2B. Representative results are shown.

Mentions: To further confirm the promoter CGI hypermethylation-mediated FBLN1 silencing in primary gastric carcinomas, FBLN1 expression and FBLN1 promoter methylation in primary gastric carcinoma tissues, adjacent non-tumour gastric tissues and normal gastric tissues were analysed by quantitative real-time RT–PCR and MSP, respectively. Fibulin 1 expression was significantly downregulated in most of the tumour tissues compared with adjacent non-tumour tissues (Figure 3A). In addition, promoter methylation was frequently detected in tumour samples but not in adjacent non-tumour and normal gastric tissue samples (Figure 3B), highlighting a tumour-specific hypermethylation of the FBLN1 promoter. There was no significant association between FBLN1 methylation and clinical characteristics such as age, gender, Helicobacter pylori infection, tumour grade, Lauren classification and differentiation (Table 1).


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)

Fibulin 1 is downregulated and hypermethylated in primary gastric carcinoma tissues. (A) The expression of FBLN1 in gastric carcinoma and adjacent non-tumour tissues was determined by quantitative real-time RT–PCR as in Figure 1A. (B) The methylation status of the FBLN1 promoter in primary gastric carcinoma and adjacent non-tumour tissues was determined by MSP as in Figure 2B. Representative results are shown.
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Related In: Results  -  Collection

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fig3: Fibulin 1 is downregulated and hypermethylated in primary gastric carcinoma tissues. (A) The expression of FBLN1 in gastric carcinoma and adjacent non-tumour tissues was determined by quantitative real-time RT–PCR as in Figure 1A. (B) The methylation status of the FBLN1 promoter in primary gastric carcinoma and adjacent non-tumour tissues was determined by MSP as in Figure 2B. Representative results are shown.
Mentions: To further confirm the promoter CGI hypermethylation-mediated FBLN1 silencing in primary gastric carcinomas, FBLN1 expression and FBLN1 promoter methylation in primary gastric carcinoma tissues, adjacent non-tumour gastric tissues and normal gastric tissues were analysed by quantitative real-time RT–PCR and MSP, respectively. Fibulin 1 expression was significantly downregulated in most of the tumour tissues compared with adjacent non-tumour tissues (Figure 3A). In addition, promoter methylation was frequently detected in tumour samples but not in adjacent non-tumour and normal gastric tissue samples (Figure 3B), highlighting a tumour-specific hypermethylation of the FBLN1 promoter. There was no significant association between FBLN1 methylation and clinical characteristics such as age, gender, Helicobacter pylori infection, tumour grade, Lauren classification and differentiation (Table 1).

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