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Galectin-7 is epigenetically-regulated tumor suppressor in gastric cancer.

Kim SJ, Hwang JA, Ro JY, Lee YS, Chun KH - Oncotarget (2013)

Bottom Line: Immunohistochemical staining using a tissue microarray of gastric cancer patients revealed significantly low expression levels of galectin-7 in malignant tissues compared with matched normal tissues, and decreased expression of galectin-7 in malignant tissues was associated with advanced TMN stage disease (p=0.034).More than 70% hypermethylation was observed in 7 of 9 gastric cancer cell lines tested and 5-aza-cytidine treatment lowered galectin-7 expression by reducing methylation in 24 cancer cell lines from five different organ origins.Further study of galectin-7 regulation may lead to improved gastric cancer diagnosis and therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea.

ABSTRACT
Gastric cancer is the second leading cause of cancer death and remains a major clinical challenge due to poor prognosis and limited treatment options. Therefore, the basic mechanisms underlying gastric tumorigenesis deserve investigation. Although regulation of the galactoside-binding lectin galectin-7 in cancer has been studied, its role in tumor formation and progression remains controversial. In this study, we investigated galectin-7 expression and its role in gastric cancer. Immunohistochemical staining using a tissue microarray of gastric cancer patients revealed significantly low expression levels of galectin-7 in malignant tissues compared with matched normal tissues, and decreased expression of galectin-7 in malignant tissues was associated with advanced TMN stage disease (p=0.034). Importantly, low expression of galectin-7 in normal tissues was associated with a poor survival rate (p=0.0561). Over-expression of galectin-7 in AGS gastric adenocarcinoma cells suppressed cell proliferation, migration, and invasion, whereas ablation of galectin-7 in KATO III gastric carcinoma cells reversed these properties. AGS cells that overexpressed galectin-7 could not form gastric tumors in xenografted mice. More than 70% hypermethylation was observed in 7 of 9 gastric cancer cell lines tested and 5-aza-cytidine treatment lowered galectin-7 expression by reducing methylation in 24 cancer cell lines from five different organ origins. We analyzed CpG islands in the galectin-7 genomic region and detected hypermethylation at +1566bp of exon 2, the predicted p53 binding region. DNA hypermethylation of this region was also detected in gastric cancer tissues from 20 patients. Taken together, our data indicate that galectin-7 has a tumor suppressive function, and that the gene is epigenetically modified by DNA methylation and significantly down-regulated in gastric cancer. Further study of galectin-7 regulation may lead to improved gastric cancer diagnosis and therapy.

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Related in: MedlinePlus

Up-regulation of galectin-7 expression in various cancer cell lines(A-B) mRNA expression of galectin-7 in 26 cancer cell lines detected by RT-PCR (A) and RT-qPCR (B). β-actin was used as a loading control. (C) MSP analysis of the galectin-7 gene in 14 cancer cell lines. The methylated (M) and unmethylated (U) DNA was amplified using primers specific for each methylation status. Universal methylated DNA was used as a positive loading control.
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Figure 6: Up-regulation of galectin-7 expression in various cancer cell lines(A-B) mRNA expression of galectin-7 in 26 cancer cell lines detected by RT-PCR (A) and RT-qPCR (B). β-actin was used as a loading control. (C) MSP analysis of the galectin-7 gene in 14 cancer cell lines. The methylated (M) and unmethylated (U) DNA was amplified using primers specific for each methylation status. Universal methylated DNA was used as a positive loading control.

Mentions: To further determine the importance of DNA methylation in the regulation of galectin-7 gene expression in various tumor cells, we treated 26 cancer cell lines from five different organ origins with 50 nmol/L 5-Aza-dC and performed RT-PCR analysis (Figure 6A) and real-time RT-PCR analysis (Figure 6B). Galectin-7 expression levels in various tumor cell lines markedly increased following treatment with 5-aza-dC as listed in Supplementary table 1. From the 26 cell lines we choose 6 breast cancer cell line and 8 lung cancer cell lines for MS-PCR analysis. As shown in Figure 6C, the test region of galectin-7 was hypermethylated in these cancer cell lines. Taken together, our results indicate that galectin-7 expression is regulated by DNA methylation in various cancer cell lines from different organ origins, including gastric cancer cell lines.


Galectin-7 is epigenetically-regulated tumor suppressor in gastric cancer.

Kim SJ, Hwang JA, Ro JY, Lee YS, Chun KH - Oncotarget (2013)

Up-regulation of galectin-7 expression in various cancer cell lines(A-B) mRNA expression of galectin-7 in 26 cancer cell lines detected by RT-PCR (A) and RT-qPCR (B). β-actin was used as a loading control. (C) MSP analysis of the galectin-7 gene in 14 cancer cell lines. The methylated (M) and unmethylated (U) DNA was amplified using primers specific for each methylation status. Universal methylated DNA was used as a positive loading control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824540&req=5

Figure 6: Up-regulation of galectin-7 expression in various cancer cell lines(A-B) mRNA expression of galectin-7 in 26 cancer cell lines detected by RT-PCR (A) and RT-qPCR (B). β-actin was used as a loading control. (C) MSP analysis of the galectin-7 gene in 14 cancer cell lines. The methylated (M) and unmethylated (U) DNA was amplified using primers specific for each methylation status. Universal methylated DNA was used as a positive loading control.
Mentions: To further determine the importance of DNA methylation in the regulation of galectin-7 gene expression in various tumor cells, we treated 26 cancer cell lines from five different organ origins with 50 nmol/L 5-Aza-dC and performed RT-PCR analysis (Figure 6A) and real-time RT-PCR analysis (Figure 6B). Galectin-7 expression levels in various tumor cell lines markedly increased following treatment with 5-aza-dC as listed in Supplementary table 1. From the 26 cell lines we choose 6 breast cancer cell line and 8 lung cancer cell lines for MS-PCR analysis. As shown in Figure 6C, the test region of galectin-7 was hypermethylated in these cancer cell lines. Taken together, our results indicate that galectin-7 expression is regulated by DNA methylation in various cancer cell lines from different organ origins, including gastric cancer cell lines.

Bottom Line: Immunohistochemical staining using a tissue microarray of gastric cancer patients revealed significantly low expression levels of galectin-7 in malignant tissues compared with matched normal tissues, and decreased expression of galectin-7 in malignant tissues was associated with advanced TMN stage disease (p=0.034).More than 70% hypermethylation was observed in 7 of 9 gastric cancer cell lines tested and 5-aza-cytidine treatment lowered galectin-7 expression by reducing methylation in 24 cancer cell lines from five different organ origins.Further study of galectin-7 regulation may lead to improved gastric cancer diagnosis and therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea.

ABSTRACT
Gastric cancer is the second leading cause of cancer death and remains a major clinical challenge due to poor prognosis and limited treatment options. Therefore, the basic mechanisms underlying gastric tumorigenesis deserve investigation. Although regulation of the galactoside-binding lectin galectin-7 in cancer has been studied, its role in tumor formation and progression remains controversial. In this study, we investigated galectin-7 expression and its role in gastric cancer. Immunohistochemical staining using a tissue microarray of gastric cancer patients revealed significantly low expression levels of galectin-7 in malignant tissues compared with matched normal tissues, and decreased expression of galectin-7 in malignant tissues was associated with advanced TMN stage disease (p=0.034). Importantly, low expression of galectin-7 in normal tissues was associated with a poor survival rate (p=0.0561). Over-expression of galectin-7 in AGS gastric adenocarcinoma cells suppressed cell proliferation, migration, and invasion, whereas ablation of galectin-7 in KATO III gastric carcinoma cells reversed these properties. AGS cells that overexpressed galectin-7 could not form gastric tumors in xenografted mice. More than 70% hypermethylation was observed in 7 of 9 gastric cancer cell lines tested and 5-aza-cytidine treatment lowered galectin-7 expression by reducing methylation in 24 cancer cell lines from five different organ origins. We analyzed CpG islands in the galectin-7 genomic region and detected hypermethylation at +1566bp of exon 2, the predicted p53 binding region. DNA hypermethylation of this region was also detected in gastric cancer tissues from 20 patients. Taken together, our data indicate that galectin-7 has a tumor suppressive function, and that the gene is epigenetically modified by DNA methylation and significantly down-regulated in gastric cancer. Further study of galectin-7 regulation may lead to improved gastric cancer diagnosis and therapy.

Show MeSH
Related in: MedlinePlus