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Implication of Leptin-Signaling Proteins and Epstein-Barr Virus in Gastric Carcinomas.

Choi E, Byeon SJ, Kim SH, Lee HJ, Kwon HJ, Ahn H, Kim DH, Chang MS - PLoS ONE (2015)

Bottom Line: Additionally, in stomach cancer cells, cleaved caspase 3 level increased by leptin-receptor inhibition, that is, apoptosis increased.Interestingly, EBV-positive AGC (n = 29) tended to show better survival of patients than EBV-negative AGC (n = 178) (P = 0.06). pAkt expression was related with a good survival of 32 patients (9%) in the EBV-positive subgroup, but was not an independent prognostic factor.The leptin-receptor may predict poor patient prognosis in the AGC, Lauren diffuse and lymph node metastasis subgroups, while EBV-positive status can show a good prognosis in the AGC.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT
We investigated the clinicopathological implications of leptin-signaling proteins and Epstein-Barr virus (EBV)-infection status in gastric carcinomas. Immunohistochemistry for leptin signalling-related proteins (leptin, leptin-receptor, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha), and in situ hybridization for EBV-encoded small RNAs was performed in 343 cases of gastric carcinomas. The siRNA against leptin-receptor was transfected into three stomach cancer cell lines, and western blot for caspase 3 was performed. The TNM stage was a prognostic factor in all 343 patients, and was negatively correlated with expression of leptin, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha (P < 0.05). Leptin-receptor expression was correlated with poor survival in 207 patients of the advanced gastric cancer (AGC) subgroup, 139 of the Lauren diffuse group, and in 160 patients with lymph node metastasis (P < 0.05, respectively). Additionally, in stomach cancer cells, cleaved caspase 3 level increased by leptin-receptor inhibition, that is, apoptosis increased. Interestingly, EBV-positive AGC (n = 29) tended to show better survival of patients than EBV-negative AGC (n = 178) (P = 0.06). pAkt expression was related with a good survival of 32 patients (9%) in the EBV-positive subgroup, but was not an independent prognostic factor. Among, leptin signaling-related proteins, expressions of leptin-receptor and mTOR were different between EBV-positive subgroup and EBV-negative subgroup (P < 0.05, respectively). In conclusion, leptin-signaling proteins and EBV status show different significance on patient survival, according to subsets of gastric carcinomas. The leptin-receptor may predict poor patient prognosis in the AGC, Lauren diffuse and lymph node metastasis subgroups, while EBV-positive status can show a good prognosis in the AGC. Each leptin signaling-related protein may be differently involved in carcinogenesis of EBV-negative and EBV-positive subsets.

No MeSH data available.


Related in: MedlinePlus

Effect of leptin-receptor inhibition in gastric carcinoma cells.Leptin-receptor in total cell lysate was inhibited by siRNA against leptin-receptor (50 μM). Cleaved caspase 3 (p11, p17 and p20 subunits) was remarkably increased in gastric carcinoma cell lines transfected with siRNA against leptin-receptor, comparing to each original cell line and each scrambled siRNA-treated cell line. The beta-actin was loading controls. ‘Si scramble’ means cells transfected with scrambled siRNA, and ‘Si Leptin-R,’ cells transfected with siRNA against leptin-receptor.
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pone.0130839.g003: Effect of leptin-receptor inhibition in gastric carcinoma cells.Leptin-receptor in total cell lysate was inhibited by siRNA against leptin-receptor (50 μM). Cleaved caspase 3 (p11, p17 and p20 subunits) was remarkably increased in gastric carcinoma cell lines transfected with siRNA against leptin-receptor, comparing to each original cell line and each scrambled siRNA-treated cell line. The beta-actin was loading controls. ‘Si scramble’ means cells transfected with scrambled siRNA, and ‘Si Leptin-R,’ cells transfected with siRNA against leptin-receptor.

Mentions: In three gastric carcinoma cell lines, transfection of siRNA against leptin-receptor resulted in a remarkable increase of cleaved caspase 3 (p11, p17 and p20 subunits), comparing to each original cells and each scrambled siRNA-transfected cells (Fig 3). In other words, leptin-receptor is suggested to prevent apoptosis in gastric carcinoma cells.


Implication of Leptin-Signaling Proteins and Epstein-Barr Virus in Gastric Carcinomas.

Choi E, Byeon SJ, Kim SH, Lee HJ, Kwon HJ, Ahn H, Kim DH, Chang MS - PLoS ONE (2015)

Effect of leptin-receptor inhibition in gastric carcinoma cells.Leptin-receptor in total cell lysate was inhibited by siRNA against leptin-receptor (50 μM). Cleaved caspase 3 (p11, p17 and p20 subunits) was remarkably increased in gastric carcinoma cell lines transfected with siRNA against leptin-receptor, comparing to each original cell line and each scrambled siRNA-treated cell line. The beta-actin was loading controls. ‘Si scramble’ means cells transfected with scrambled siRNA, and ‘Si Leptin-R,’ cells transfected with siRNA against leptin-receptor.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493019&req=5

pone.0130839.g003: Effect of leptin-receptor inhibition in gastric carcinoma cells.Leptin-receptor in total cell lysate was inhibited by siRNA against leptin-receptor (50 μM). Cleaved caspase 3 (p11, p17 and p20 subunits) was remarkably increased in gastric carcinoma cell lines transfected with siRNA against leptin-receptor, comparing to each original cell line and each scrambled siRNA-treated cell line. The beta-actin was loading controls. ‘Si scramble’ means cells transfected with scrambled siRNA, and ‘Si Leptin-R,’ cells transfected with siRNA against leptin-receptor.
Mentions: In three gastric carcinoma cell lines, transfection of siRNA against leptin-receptor resulted in a remarkable increase of cleaved caspase 3 (p11, p17 and p20 subunits), comparing to each original cells and each scrambled siRNA-transfected cells (Fig 3). In other words, leptin-receptor is suggested to prevent apoptosis in gastric carcinoma cells.

Bottom Line: Additionally, in stomach cancer cells, cleaved caspase 3 level increased by leptin-receptor inhibition, that is, apoptosis increased.Interestingly, EBV-positive AGC (n = 29) tended to show better survival of patients than EBV-negative AGC (n = 178) (P = 0.06). pAkt expression was related with a good survival of 32 patients (9%) in the EBV-positive subgroup, but was not an independent prognostic factor.The leptin-receptor may predict poor patient prognosis in the AGC, Lauren diffuse and lymph node metastasis subgroups, while EBV-positive status can show a good prognosis in the AGC.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT
We investigated the clinicopathological implications of leptin-signaling proteins and Epstein-Barr virus (EBV)-infection status in gastric carcinomas. Immunohistochemistry for leptin signalling-related proteins (leptin, leptin-receptor, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha), and in situ hybridization for EBV-encoded small RNAs was performed in 343 cases of gastric carcinomas. The siRNA against leptin-receptor was transfected into three stomach cancer cell lines, and western blot for caspase 3 was performed. The TNM stage was a prognostic factor in all 343 patients, and was negatively correlated with expression of leptin, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha (P < 0.05). Leptin-receptor expression was correlated with poor survival in 207 patients of the advanced gastric cancer (AGC) subgroup, 139 of the Lauren diffuse group, and in 160 patients with lymph node metastasis (P < 0.05, respectively). Additionally, in stomach cancer cells, cleaved caspase 3 level increased by leptin-receptor inhibition, that is, apoptosis increased. Interestingly, EBV-positive AGC (n = 29) tended to show better survival of patients than EBV-negative AGC (n = 178) (P = 0.06). pAkt expression was related with a good survival of 32 patients (9%) in the EBV-positive subgroup, but was not an independent prognostic factor. Among, leptin signaling-related proteins, expressions of leptin-receptor and mTOR were different between EBV-positive subgroup and EBV-negative subgroup (P < 0.05, respectively). In conclusion, leptin-signaling proteins and EBV status show different significance on patient survival, according to subsets of gastric carcinomas. The leptin-receptor may predict poor patient prognosis in the AGC, Lauren diffuse and lymph node metastasis subgroups, while EBV-positive status can show a good prognosis in the AGC. Each leptin signaling-related protein may be differently involved in carcinogenesis of EBV-negative and EBV-positive subsets.

No MeSH data available.


Related in: MedlinePlus