Expression of tumor necrosis factor-α-induced protein 8 in stage III gastric cancer and the correlation with DcR3 and ERK1/2

Abstract

Abstract. Tumor necrosis factor (TNF)-α-induced protein 8 (TIPE) is a recently identified protein that is considered to be associated with various malignancies, including esophageal, breast and pancreatic cancer; however, the importance of TIPE in gastric cancer (GC) remains unknown. Decoy receptor 3 (DcR3) is a member of the tumor necrosis factor receptor superfamily that is expressed in digestive system neoplasms. The expression of DcR3 is regulated by the mitogen-activated protein kinase (MAPK)/MAPK kinase/extracellular signal-regulated kinase (ERK) signaling pathway. Reverse transcription-polymerase chain reaction was performed to detect the expression of TIPE, ERK and DcR3 in the pathological and tumor-adjacent normal gastric tissues of 30 patients that demonstrated stage III gastric adenocarcinoma. The expression and distribution of the TIPE protein was examined using immunohistochemistry, and the clinical significance and expression levels of DcR3 and ERK1/2 were evaluated. The expression of TIPE, ERK1/2 and DcR3 in the tumor tissues of GC was significantly increased compared with paracarcinoma tissues (P<0.05). In addition, TIPE expression positively correlated with DcR3 and ERK1 levels (r= 0.538 and r=0.462, respectively; P<0.05). There was no statistical difference between tumor tissues from patients with varying age, gender, differentiation or lymph node metastasis (P>0.05). TIPE may be vital in the progression of GC. TIPE may be associated with the expression of DcR3 and ERK1/2, which may be involved in the cell apoptosis of GC. The present study elucidates the potential function of TIPE as a novel marker and therapeutic target for GC.

<p>Case–Control Study on <em>TNFRSF6B</em> Gene Polymorphism and Susceptibility to Gastric Cancer in a Chinese Han Population</p>

“…Edfeldt et al 23 found that TNFRSF6B is related to poor survival and can be considered as a marker for liver metastases. Hu et al 24 showed that the expression of DcR3 is higher in the tumor tissues of GC than in paracarcinoma tissues and that TNFRSF6B is important in assessing the stage of GC. Currently, studies on TNFRSF6B polymorphisms are rare.…”

TIPE attenuates the apoptotic effect of radiation and cisplatin and promotes tumor growth via JNK and p38 activation in Raw264.7 and EL4 cells

“…As prolonged JNK phosphorylation uncouples MEK-mediated ERK activation in a c-Jun-dependent manner (29), opposing effects of ERK and JNK-p38 MAPKs on apoptosis have been found in nerve growth factor withdrawal cells (30). Meanwhile, TIPE expression was found to be positively correlated with ERK1 but not ERK2 as documented in gastric cancer (31). Hence, the exact function of MEK phosphorylation in TIPE-mediated promotion of tumor formation remains unclear and needs further elucidation.…”

The role of the TNF receptors and apoptosis inducing ligands in tumor growth

“…The expression of DcR3 is regulated by the mitogen-activated protein kinase (MAPK)/MAPK kinase/extracellular signal-regulated kinase (ERK) signaling pathway. The expression of TNFA-induced protein 8, ERK1/2 and DcR3 in the tumor tissues of GC was significantly increased compared with paracarcinoma tissues and TNFA-induced protein 8 expression positively correlated with DcR3 and ERK1/2 levels, which may be involved in the cell apoptosis of gastric and pancreatic cancer [55,56].…”

“…These fibroblasts interact with collagen matrix, and aberrantly activated Akt increases DcR3 expression and protects these cells from the FasL-dependent apoptotic pathway. TNFRSF6B is also induced by TNFA-induced protein 8, a recently identified protein that is considered to be associated with various malignancies, including esophageal, breast, gastric, and pancreatic cancer [55]. The expression of DcR3 is regulated by the mitogen-activated protein kinase (MAPK)/MAPK kinase/extracellular signal-regulated kinase (ERK) signaling pathway.…”