Abstract
BackgroundGastrokine-1 (GKN1), a secreted protein, is specifically expressed in gastric mucosa to protect and maintain the integrity of gastric epithelium. The present study investigated differential expression of GKN1 in normal, precancerous, and cancerous gastric tissues, and explored the biological functions of GKN1 protein in gastric cancer cells.MethodsRT-PCR, Western blot, and immunohistochemistry were performed to detect GKN1 expression in normal, precancerous, cancerous gastric tissues and seven gastric cancer cell lines. Gene transfection was used to restore GKN1 expression in gastric cancer AGS cells. Phenotypic changes (i.e., cell viability, apoptosis, cell cycle modulation, and sensitivity of gastric cancer cells to fluorouracil (5-FU)) were assayed in the transfected cells. DNA microarrays were used to analyze expression changes of apoptosis-related genes.ResultsSignificant downregulation or absence of GKN1 expression in seven gastric cancer cell lines were detected and progressive decrease of GKN1 expression from normal mucosa, precancerous tissue, to cancer tissues was observed. Moreover, restoration of GKN1 expression suppressed gastric cancer cell viability and induced the cells to undergo apoptosis. GKN1 expression also enhanced tumor cell sensitivity to 5-FU treatment. Moreover, it was found that GKN1 expression in AGS cells modulated expression of 19 apoptosis-related genes.ConclusionsExpression of GKN1 is progressively lost from normal mucosa, precancerous to cancerous gastric tissues, while restoration of GKN1 expression induces gastric cancer cells to undergo apoptosis, and enhances sensitivity of gastric cancer cells to 5-FU-induced apoptosis.
Highlights
Gastrokine-1 (GKN1), a secreted protein, is expressed in gastric mucosa to protect and maintain the integrity of gastric epithelium
We found that GKN1 mRNA was weakly expressed in gastric cancer MKN 28 cells, and was absence in AGS, N87, MKN45, SNU16, SNU1, and KATO cells (Figure 1A)
We found that the GKN1 protein was abundantly expressed in the upper glandular layer of the top one third superficial epithelium, while expression of GKN1 protein was progressively down regulated from normal gastric mucosa, atrophic gastritis, intestinal metaplasia and dysplasia, to gastric cancer (Table 2) (Figure 2)
Summary
Gastrokine-1 (GKN1), a secreted protein, is expressed in gastric mucosa to protect and maintain the integrity of gastric epithelium. The GKN1 protein is downregulated in comparison to abundant expression in normal gastric mucosa [5] This protein may be a potential biological marker for early detection of gastric cancer. Several studies observed that GKN1 expression was down regulation in gastric atrophy and intestinal metaplastic lesions and even absence in gastric cancer [5,11]. These studies demonstrate that GKN1 may play a key role in the gastric cancer progression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Journal of Experimental & Clinical Cancer Research
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
