Molecular expression of Gastrokine 1 in normal mucosa and in Helicobacter pylori-related preneoplastic and neoplastic gastric lesions

Abstract

We have analyzed the expression of Gastrokine 1 (GKN1), one of the most abundant protein of gastric mucosa, in Helicobacter pylori-related preneoplastic and neoplastic gastric lesions.The GKN1 expression was downregulated in 36 H. pyloripositive patients with respect to 29 H. pylori-negative subjects as evaluated by Western blot, reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry, showing a progressive decrease from chronic gastritis to atrophy and intestinal metaplasia. Interestingly, in gastric cancer (GC) patients, GKN1 was undetectable in tissue tumoral areas but was instead expressed in the corresponding tissue non-tumoral areas. In conclusion our data suggests that GKN1 expression is related to the inflammatory damage of gastric mucosa and could be the related to the gastric cellular phenotype.

Role of Gastrokine 1 in Gastric Cancer

“…We also analyzed the expression of GKN1 in human specimens derived from patients with gastric cancer. With respect to the non-tumoral area, it was observed that GKN1 expression was consistently down regulated or absent in tumoral area (Nardone et al, 2008). The 28 patients with Gastric Cancer (GC) (20 intestinal and 8 diffuse) showed the following characteristics: the intestinal type was well differentiated in 4, moderately differentiated in 8 Fig.…”

“…Such interaction could be important in the regulation of the integrity of the mucosa (Bruce et al, 2005;Otto et al, 2006;Baus-Loncar et al, 2007). The strong down-regulation of GKN1 expression in patients with H. pylori infection its absence in gastric cancer (Nardone et al, 2008;Moss et al, 2008) and its absence in human gastric cancer cell lines (AGS and MKN28) (Motoyama et al, 1986;Segal et al, 1996;Oien et al, 2004) are factors that suggest the participation of GKN1 in the host response to H. pylori and suggest also that GNN1 can act as gastric tumor suppressor gene (Du et al, 2003). Regarding this point, since GKN1 is highly down-regulated or absent in gastric cancer, one possible explanation of its disappearance could be linked to epigenetic events or loss of heterozygosity, as it was observed for other tumor suppressor genes such as TFF1 (Carvalho et al, 2002).…”

Gastritis and Peptic Ulcer Diseases in Dogs: A Review

“…The NSAIDs inhibits the enzyme COX which is involved in the prostaglandin synthesis, and inhibit the synthesis of prostacyclin and prostaglandin E, resulting in the loss of the gastric protective mechanism (Enberg et al, 2006). If any change on the expression of GKN gene leads to the deficiency of GKN1 & GKN2, results have been reported as gastric inflammation, non-steroidal antiinflammatory (NSAID) induced mucosal injury and the development of neoplasia of gastric mucosa Nardone et al, 2008). Another factor concerned with the pathogenesis of NSAID-induced gastric disorder is peroxidation of lipids of cell membranes and damage to the cellular proteins by the formation of oxidative free radicals and proteases from activated neutrophils (Biswas et al, 2003).…”

“…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). …”

Down-Regulation of GKN1 in Gastric Cancer Is Not Associated with the RUNX3 Expression

“…The characterization of the non-tumoral gastric mucosa was made by the hospital pathologist from the comparison between the macroscopic aspects of normal tissue versus the tumoral one [23], and from our finding clearly indicating that GKN1, highly expressed in gastric non-tumoral tissues, was strongly down-regulated or totally absent in GC tissues [4]. The University of Naples Federico II Ethics Committee (Comitato Etico Università Federico II) approved this study (protocol number 34/15) [23].…”