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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 functions as a tumour suppressor gene in gastric cancer cell line MKN45. The effect of ectopic FBLN1 expression on tumour cell growth was investigated by the monolayer colony-formation assay (A). Quantitative analyses of colony numbers are shown in the right panel as values of mean±standard deviation. P-values were calculated using Student's t-test. The asterisk indicates statistically significant difference (P<0.01). The expression of FBLN1 after transfection was confirmed by western blotting analysis (B). (C) The rate of apoptosis before and after FBLN1 expression was determined by flow cytometry. Values are shown as mean±s.d. from triplicate experiments. P-values were calculated using Student's t-test. The asterisk indicates statistically significant difference (P<0.01).
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fig4: Fibulin 1 functions as a tumour suppressor gene in gastric cancer cell line MKN45. The effect of ectopic FBLN1 expression on tumour cell growth was investigated by the monolayer colony-formation assay (A). Quantitative analyses of colony numbers are shown in the right panel as values of mean±standard deviation. P-values were calculated using Student's t-test. The asterisk indicates statistically significant difference (P<0.01). The expression of FBLN1 after transfection was confirmed by western blotting analysis (B). (C) The rate of apoptosis before and after FBLN1 expression was determined by flow cytometry. Values are shown as mean±s.d. from triplicate experiments. P-values were calculated using Student's t-test. The asterisk indicates statistically significant difference (P<0.01).

Mentions: Current data indicate that FBLN1 might have a tumour suppressive function. We investigated its tumour suppressive function by a gain-of-function strategy with the monolayer colony-formation assay. After re-expression of FBLN1 in MKN45 cells, the number of colonies formed on the plate was significantly reduced (P<0.01) (Figure 4A and B). The growth inhibition was caused by an increase in cell apoptosis, as the numbers of cells with sub-G1 distribution increased significantly after FBLN1 re-expression (Figure 4C).


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 functions as a tumour suppressor gene in gastric cancer cell line MKN45. The effect of ectopic FBLN1 expression on tumour cell growth was investigated by the monolayer colony-formation assay (A). Quantitative analyses of colony numbers are shown in the right panel as values of mean±standard deviation. P-values were calculated using Student's t-test. The asterisk indicates statistically significant difference (P<0.01). The expression of FBLN1 after transfection was confirmed by western blotting analysis (B). (C) The rate of apoptosis before and after FBLN1 expression was determined by flow cytometry. Values are shown as mean±s.d. from triplicate experiments. P-values were calculated using Student's t-test. The asterisk indicates statistically significant difference (P<0.01).
© Copyright Policy
Related In: Results  -  Collection

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

fig4: Fibulin 1 functions as a tumour suppressor gene in gastric cancer cell line MKN45. The effect of ectopic FBLN1 expression on tumour cell growth was investigated by the monolayer colony-formation assay (A). Quantitative analyses of colony numbers are shown in the right panel as values of mean±standard deviation. P-values were calculated using Student's t-test. The asterisk indicates statistically significant difference (P<0.01). The expression of FBLN1 after transfection was confirmed by western blotting analysis (B). (C) The rate of apoptosis before and after FBLN1 expression was determined by flow cytometry. Values are shown as mean±s.d. from triplicate experiments. P-values were calculated using Student's t-test. The asterisk indicates statistically significant difference (P<0.01).
Mentions: Current data indicate that FBLN1 might have a tumour suppressive function. We investigated its tumour suppressive function by a gain-of-function strategy with the monolayer colony-formation assay. After re-expression of FBLN1 in MKN45 cells, the number of colonies formed on the plate was significantly reduced (P<0.01) (Figure 4A and B). The growth inhibition was caused by an increase in cell apoptosis, as the numbers of cells with sub-G1 distribution increased significantly after FBLN1 re-expression (Figure 4C).

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