Expression Of C-met In Gastric And Gastric Remnant Cancer And The Effect Of NK4 On Its Expression

Objective1. To investigate the expression of c-met in gastric cancer cells and specimen of gastric cancer both in mRNA and protein levels and its roles in the pathogenesis of gastric cancer.2. To find the modulation effect of a variant of hepatocyte growth factor, NK4 on the expression of c-met in gastric cancer cells and subsequent effect on the apoptosis in gastric cancer cells.Methods1. RT-PCR and Western blot were employed to detect the expression of c-met in 2 gastric cancer cell lines:SGC-7901,BGC-823 and 53 specimen of gastric cancer and matched normal mucosa.2. The immunohistochemistry technique was applied to examine the expression of c-met protein in 53 specimen of gastric cancer and pared normal mucosa and 34 specimen of gastric remnant cancer.3. Flow cytometry and MTT assay were employed to detect the expression of c-met and its effect on apoptosis in SGC-7901 and BGC-823 cell lines pretreated with NK4, a variant of hepatocyte growth factor in different concentration.Results1. c-met mRNA and protein was positively expressed in SGC-7901 and BGC-823 cell lines. All specimen of gastric cancer expressed c-met transcripts.2. c-met protein expression of variable intensity and extend was detected in the normal gastric mucosa and adenocarcinomas in gastric cancer and gastric remnant cancer. The positive expression scores in normal mucosa was 22.64%(12/53), 75.47%(40/53)of gastric cancer expressed c-met more intensely and extensively than matched normal gastric mucosa, which was statistically significant(p<0.01).The stained pattern of all cases were graded as followed: +28.30%(15/53), ++30.19%(16/53), + + +16.98%(9/53). The positive expression scores in gastric remnant cancer was 82.35%(28/34), and the stained pattern were+29.41 %(10/34), ++35.29%(12/34), + + + 17.65%(6/34), respectively. The extent of c-met expression in tumors was independent of pathomorphology, tumor stage, hepatic metastasis and dependent of degree of differentiation (p<0.05), lymph metastasis(p<0.05) in gastric carcinoma. The extent of c-met expression in tumors was independent of rejunction, pathomorphology and dependent of tumor stage (p<0.05), differentiation (p<0.05), lymph metastasis(p<0.05), hepatic metastasis(p<0.05) and the interval between two operations (p<0.05) in gastric remnant carcinoma.3. The c-met expression could not be decreased by 100ug/ml NK4 in SGC-7901 and BGC-823 cell lines. After incubated with NK4(20,40,60,80,100ug/ml) for 24h and 48h, it can induce 37.4% apoptosis of SGC-7901 cells and 43.4% apoptosis of BGC-823 cells at the most.Conclusion1. c-met was expressed in SGC-7901 and BGC-823 cell lines and the specimen of gastric adenocarcinomas and matched normal mucosa and gastric remnant adenocarcinomas. The expression level of c-met in adenocarcinomas was much higher than that in pared normal mucosa. Over-expression of c-met was a tumor-specific phenomenon, which can provide that c-met was a new oncogenesis with high expression in gastric and gastric remnant cancer.2. NK4, a variant of hepatocyte growth factor, can link to c-met, but it can not activate the receptor. NK4 can induce apoptosis in gastric cancer cell. So NK4 may become a new target in gastric cancer and gastric remnant cancer management.