Abstract
GKN2 (gastrokine 2) mainly plays a regulatory role in gastric mucosal defense and cell protection mechanisms, and its role in gastric cancer has not been thoroughly elucidated. Immunohistochemistry was used to detect GKN2 and TFF1 expressions in 90 gastric cancer tissues, 48 neoplastic resection margins, and 22 normal gastric mucosa epithelia. It showed that the downregulation of GKN2 and TFF1 expressions in gastric cancer tissues was significantly different from that in adjacent normal gastric tissues and distal gastric mucosal tissues. Nevertheless, correlation analysis showed that GKN2 expression in gastric cancer tissues was independent of TFF1 expression. After overexpression of GKN2 was constructed in human gastric cancer cell line MKN28 with the Ad-GFP-GKN2 transfected, cell viability was measured by CCK-8 assay, and migration and invasion ability were analyzed by transwell migration assay and transwell invasion assay. It indicated that overexpression of GKN2 significantly reduced the viability of MKN28 and SGC7901 cells. Overexpression of GKN2 could also inhibit the migration and invasion ability in MKN28 and SGC7901 cells. In addition, upregulation of GKN2 can inactivate the JAK2/STAT3 pathway. Our data suggest that GKN2 and TFF1 play the antitumor role in gastric carcinoma, and TFF1 may not interact or cooperate with GKN2. GKN2 overexpression can inhibit the growth and metastasis by downregulating the JAK2/STAT3 pathway in gastric cancer cells.
Highlights
Gastric cancer (GC) has a high incidence in the population of our country and ranks high in mortality among many cancers [1]. e development of gastric cancer is a complex process of multistage and multistep
GKN1 and TFF1 were highly expressed in distal gastric mucosa (DGM) but less in paracancerous tissue (PT)
Association between Expression of GKN2 and TFF1 in Gastric Carcinoma Tissues. It showed that six cases of GKN2 protein-positive expression include three cases of TFF1positive expression in gastric cancer specimens, while 71 cases of trefoil factor 1- (TFF1-)negative expression exist concurrently with 68 cases of GKN2-negative expression, namely, TFF1 protein expression loss is related to GKN2 protein expression loss as given in Table 3. e relationship between the two protein expressions seems to be a positive correlation (r ≈ ≈0.96), but statistics analysis showed the difference is meaningless (p 0.074)
Summary
Gastric cancer (GC) has a high incidence in the population of our country and ranks high in mortality among many cancers [1]. e development of gastric cancer is a complex process of multistage and multistep. E development of gastric cancer is a complex process of multistage and multistep. In this process, there are many genes involved, including the regulation of cell proliferation, apoptosis, differentiation, invasion, and metastasis. There are few molecules expressed in gastric mucosa. GKN is a new family of gastrin-specific proteins, which is almost completely expressed and secreted by gastric mucosal epithelial cells. GKN1 can inhibit the metastasis of gastric cancer cells and reduce their migration and invasion ability [5]. GKN2 is downregulation or loss in gastric cancer tissues. It is reported that GKN2 affects the growth of gastric cancer cells in a trefoil factor 1- (TFF1-) dependent manner [12]. GKN2 forms disulfide-linked heterodimers with TFF1 [13, 14]
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