The Function Of HepaCAM In Gastric Adenocarcinoma

Objective:1.To determine the relationship between Hepa CAM expression and clinicopathological features of gastric cancer.2.To contruct plasmids with the specific Hepa CAM expression and transtect them into gastric cancer cells,then investigate the influence of Hepa CAM in regulating the biological characteristics of gastric cancer cells.3.To explore possible mechanisms mediated by Hepa CAM in gastric cancer.Methods:1.The expression of Hepa CAM m RNA and protein in 42 fresh specimens of gastric cancer tissues and adjacent non-cancer specimens was detected by RT-PCR、Western blot and immunohistochemistry staining.2.The expression of Hepa CAM protein in gastric cancer cells(AGS 、SGC-7901 、 BGC-823 、 MCG-803)was detected by Western blot.The stable down-regulation and over-expression of Hepa CAM in gastric cancer cells were constructed.MTT assay and colony formation assay were used to examine the effects of Hepa CAM on the growth of gastric cancer cells by crystal violet staining.Nude mice xemograft assay was used to examine the effects of Hepa CAM on the growth of gastric cancer cells in vivo.3.Gene expression array was used to investigate the changes of gene expression profile in AGS gastric cancer cells with Hepa CAM-overexpressing(AGS/con 、AGS/Hepa CAM).Differentially expressed genes were screened.RT-PCR and Western blot were used to validate the expression changes of target genes.Analyses were performed to predict some signal pathways in gastric cancer.Results:1.The expression of Hepa CAM was significantly down-regulated in most gastric adenocarcinom tissues as compared to normal tissues.2.Forced expression of Hepa CAM in SGC-7901 and BGC-823 gastric cancer cells reduced their growth in culture,whereas RNAi-mediated knock-down of Hepa CAM in AGS and MCG-803 gastric cancer cells dramatically promotes cell growth,and significantly increased tumor formation in vivo through the experiment of subcutaneous tumor formation in nude mice.3.We found that some genes in connection with EGF/EGFR pathway have dramatically changed.The expression of p-STAT3 and p-AKT473 was downregulated.Conclusions:1.The current study defined the clinical expression levels of Hepa CAM in gastric cancer and revealed that decreased Hepa CAM expression is closely related to the development of gastric cancer.2.The study revealed that Hepa CAM exerts inhibitory effects on cancer cell proliferation.3.The study found that the functions of Hepa CAM in gastric cancer may be correlation with EGF/EGFR signal pathway and its following p-STAT3 and p-AKT473 signal pathways.