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

Expression levels of galectin-7 in malignant and normal tissues of 56 gastric cancer patients(A) In situ expression of galectin-7 in normal and tumor tissue from gastric cancer patients of intestinal and diffuse type was detected by immunohistochemical (IHC) analysis and hematoxylin and eosin (H&E) staining (magnification: ×200, ×400). (B) Comparative analysis of galectin-7 expression in normal and tumor tissues of gastric cancer patients based on intensity of galectin-7 staining. p values (*, p<0.001) were calculated using Student's t-test. (C) Kaplan-Meier analysis of survival curves for patients with gastric cancer (N = 44) according to the expression of galectin-7 in normal tissues. The galectin-7 low-expression group showed a much lower survival rate at 125 months compared with the galectin-7 high-expression group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Expression levels of galectin-7 in malignant and normal tissues of 56 gastric cancer patients(A) In situ expression of galectin-7 in normal and tumor tissue from gastric cancer patients of intestinal and diffuse type was detected by immunohistochemical (IHC) analysis and hematoxylin and eosin (H&E) staining (magnification: ×200, ×400). (B) Comparative analysis of galectin-7 expression in normal and tumor tissues of gastric cancer patients based on intensity of galectin-7 staining. p values (*, p<0.001) were calculated using Student's t-test. (C) Kaplan-Meier analysis of survival curves for patients with gastric cancer (N = 44) according to the expression of galectin-7 in normal tissues. The galectin-7 low-expression group showed a much lower survival rate at 125 months compared with the galectin-7 high-expression group.

Mentions: To determine the expression levels of galectin-7 in gastric cancer patients, we prepared a tissue microarray (TMA) of 44 patients and performed immunohistochemical analysis (Table 1 and Figure 1A). Strong expression was detected in normal tissues from patients with intestinal and diffuse types of gastric cancer and most of the galectin-7 was localized in the cytosol. Expression was notably down-regulated in gastric cancer tissues (Figure 1A). Quantitative analysis of galectin-7 staining confirmed that gastric cancer patients had low or no expression in malignant tissues compared with normal tissues (Figure 1B). As shown in Table 1, we statistically analyzed the expression levels with respect to clinical factors. The protein expression levels of galectin-7 in malignant tissues were significantly decreased in patients with advanced stage disease by T classification (p=0.034) (Table 1). Moreover, the survival probability was higher in gastric cancer patients with high galectin-7 expression in normal tissues (p=0.0561) (Figure 1C) although this was not statistically significant, possibly due to the limited number of samples. Our data strongly indicate that galectin-7 is down-regulated during gastric cancer progression.


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

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

Expression levels of galectin-7 in malignant and normal tissues of 56 gastric cancer patients(A) In situ expression of galectin-7 in normal and tumor tissue from gastric cancer patients of intestinal and diffuse type was detected by immunohistochemical (IHC) analysis and hematoxylin and eosin (H&E) staining (magnification: ×200, ×400). (B) Comparative analysis of galectin-7 expression in normal and tumor tissues of gastric cancer patients based on intensity of galectin-7 staining. p values (*, p<0.001) were calculated using Student's t-test. (C) Kaplan-Meier analysis of survival curves for patients with gastric cancer (N = 44) according to the expression of galectin-7 in normal tissues. The galectin-7 low-expression group showed a much lower survival rate at 125 months compared with the galectin-7 high-expression group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Expression levels of galectin-7 in malignant and normal tissues of 56 gastric cancer patients(A) In situ expression of galectin-7 in normal and tumor tissue from gastric cancer patients of intestinal and diffuse type was detected by immunohistochemical (IHC) analysis and hematoxylin and eosin (H&E) staining (magnification: ×200, ×400). (B) Comparative analysis of galectin-7 expression in normal and tumor tissues of gastric cancer patients based on intensity of galectin-7 staining. p values (*, p<0.001) were calculated using Student's t-test. (C) Kaplan-Meier analysis of survival curves for patients with gastric cancer (N = 44) according to the expression of galectin-7 in normal tissues. The galectin-7 low-expression group showed a much lower survival rate at 125 months compared with the galectin-7 high-expression group.
Mentions: To determine the expression levels of galectin-7 in gastric cancer patients, we prepared a tissue microarray (TMA) of 44 patients and performed immunohistochemical analysis (Table 1 and Figure 1A). Strong expression was detected in normal tissues from patients with intestinal and diffuse types of gastric cancer and most of the galectin-7 was localized in the cytosol. Expression was notably down-regulated in gastric cancer tissues (Figure 1A). Quantitative analysis of galectin-7 staining confirmed that gastric cancer patients had low or no expression in malignant tissues compared with normal tissues (Figure 1B). As shown in Table 1, we statistically analyzed the expression levels with respect to clinical factors. The protein expression levels of galectin-7 in malignant tissues were significantly decreased in patients with advanced stage disease by T classification (p=0.034) (Table 1). Moreover, the survival probability was higher in gastric cancer patients with high galectin-7 expression in normal tissues (p=0.0561) (Figure 1C) although this was not statistically significant, possibly due to the limited number of samples. Our data strongly indicate that galectin-7 is down-regulated during gastric cancer 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