Overexpression of gastrokine 1 in gastric cancer cells induces Fas‐mediated apoptosis

Abstract

Gastrokine 1 (GKN1) is involved in the replenishment of the surface lumen epithelial cell layer, in maintaining the mucosal integrity, and could play a role in cell proliferation and differentiation. In fact, after injury of the gastric mucosa, restoration may occur very rapidly in the presence of GKN1. In contrast, if the protein is downregulated, the repair process may be hampered; however, application of GKN1 to gastrointestinal cells promoted epithelial restoration. Because GKN1 possesses some mitogenic effects on intestinal epithelial cells (IEC-6) whereas this protein was also capable of inhibiting proliferation in gastric cancer cells (MKN28), we decided to study its involvement in apoptosis to understand the role of GKN1 in the modulation of inflammatory damage or tumorigenesis in gastric mucosa. We found by cytofluorimetry, Western blot and RT-PCR that the overexpression of GKN1 in gastric cancer cell lines (AGS and MKN28) stimulated the expression of Fas receptor. Moreover, compared to control cells, a significant increase of apoptosis, evaluated by TUNEL, was observed when GKN1 transfected cells were treated with a monoclonal antibody (IgM) anti-Fas. The activation of Fas expression was also observed by the overexpression of GKN1 in other cancer cell lines. Moreover, in GKN1-overexpressing gastric cancer cells exposed to FasL, the activation of caspase-3 was also observed by Western blot and fluorescence assays. Our data represent the first report for GKN1 as modulator of apoptotic signals and suggest that GKN1 might play an important role for tissue repair during the early stages of neoplastic transformation.

Role of Gastrokine 1 in Gastric Cancer

“…After transfection, cell growth and apoptosis was evaluated by cytofluorimetry. The overexpression of GKN1 in MKN28 or AGS cells, with respect to control cells, reduced cell growth (Rippa et al, 2010). A similar effect was also reported by Shiozaki et al, 2001, who observed a reduction in MKN28 colony formation in cells transfected with CA11 gene with respect to control cells.…”

Gastritis and Peptic Ulcer Diseases in Dogs: A Review

“…GKN1 connected with decreasing the formation of colonies and proliferation by an atypical glandular cell of gastric mucosa and reducing of cellular viability, proliferation, and colony . GKNs and trefoil factors (TFFs) both are together lead to enhance cellular differentiation, cytoprotective role and working on NF-κβ signalling pathways that result anti-inflammatory effects, therefore it promotes restoration of gastric epithelial cells (Rippa et al, 2011). If any change on the expression of GKN gene cause deficiency of GKN1 & GKN2, results from gastric inflammation, non-steroidal antiinflammatory (NSAID) induced mucosal injury and the development of neoplasia of gastric mucosa Nardone et al, 2008).…”

Claudins, Inflammation and Epithelial-Mesenchymal Transition in Gastric Tissue

“…Resveratrol, a compound found in grapes and red wine inhibits EMT in lung cancer [127] similarly to Celastrol, also known as tripterine, that also has inhibitory effects [128]. In the early stages of gastric neoplastic transformation the overexpression of gastrokine 1 might protect against MET [129]. The use of anti-HER2 drugs is promising but apparently only in HER2-positive gastric cancer [130].…”