Limits...
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.

Show MeSH

Related in: MedlinePlus

The effect of galectin-7 over-expression on tumor growth of xenografts in nude miceAGS SQ cells (100 μl; 1 × 106 cells) in Matrigel were implanted into Balb/c-nude mice to form subcutaneous xenografts. After 8 weeks the mice were sacrificed, the tumors were photographed (A), and tumor size (B) and weight (C) were measured. The p value for tumor size and weight (* p=0.048 and 0.0234 vs. Mock groups) was calculated using Student's t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3824540&req=5

Figure 4: The effect of galectin-7 over-expression on tumor growth of xenografts in nude miceAGS SQ cells (100 μl; 1 × 106 cells) in Matrigel were implanted into Balb/c-nude mice to form subcutaneous xenografts. After 8 weeks the mice were sacrificed, the tumors were photographed (A), and tumor size (B) and weight (C) were measured. The p value for tumor size and weight (* p=0.048 and 0.0234 vs. Mock groups) was calculated using Student's t-test.

Mentions: We prepared stable galectin-7 over-expressing AGS cells and inoculated them into nude mice (Figure 4). Although tumors were formed from AGS cells expressing vector control pcDNA 3.0, the galectin-7 over-expressing AGS cells could not form gastric tumors in the xenografted mice (Figure 4). These results strongly suggest that galectin-7 prevents gastric cancer formation and progression.


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

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

The effect of galectin-7 over-expression on tumor growth of xenografts in nude miceAGS SQ cells (100 μl; 1 × 106 cells) in Matrigel were implanted into Balb/c-nude mice to form subcutaneous xenografts. After 8 weeks the mice were sacrificed, the tumors were photographed (A), and tumor size (B) and weight (C) were measured. The p value for tumor size and weight (* p=0.048 and 0.0234 vs. Mock groups) was calculated using Student's t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: The effect of galectin-7 over-expression on tumor growth of xenografts in nude miceAGS SQ cells (100 μl; 1 × 106 cells) in Matrigel were implanted into Balb/c-nude mice to form subcutaneous xenografts. After 8 weeks the mice were sacrificed, the tumors were photographed (A), and tumor size (B) and weight (C) were measured. The p value for tumor size and weight (* p=0.048 and 0.0234 vs. Mock groups) was calculated using Student's t-test.
Mentions: We prepared stable galectin-7 over-expressing AGS cells and inoculated them into nude mice (Figure 4). Although tumors were formed from AGS cells expressing vector control pcDNA 3.0, the galectin-7 over-expressing AGS cells could not form gastric tumors in the xenografted mice (Figure 4). These results strongly suggest that galectin-7 prevents gastric cancer formation and progression.

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