Smad4 Expression in Gastric Adenocarcinoma

ABSTRACT

BACKGROUND: The role of Smad4 in carcinogenesis is important, because of its function as a central mediator of TGF-beta signaling. In the present study we analyzed the expressions of Smad4 mRNA and protein in human gastric cancer cell lines and tissues and we also analyzed their clinicopathological significance. METHODS: We used semi-quantitative RT-PCR for Smad4 mRNA expression in 13 cases of fresh gastric cancer tissues and two gastric cancer cell lines (MKN-28, SNU-1). We also used immunohistochemistry for Smad4 protein expression in 88 cases of formalin fixed gastric cancers tissues. RESULTS: The mRNA level of Smad4 was higher in MKN-28 cell line (intestinal type) than in the SNU-1 cell line (diffuse type). Fresh frozen gastric cancer tissues showed that the intestinal type of gastric cancer had higher Smad4 mRNA expressions than the diffuse type of gastric cancer (p<0.05). Immunohistochemical staining for Smad4 revealed that cytoplasmic and nuclear expressions of Smad4 were significantly correlated with histologic types of gastric cancer (p<0.05). That is, the intestinal type of gastric cancer showed more cytoplasmic and nuclear smad4 expressions than did the diffuse type of gastric cancer. Reduced cytoplasmic expressions and positive nuclear expressions of Smad4 were more prominent in the advanced gastric cancer than in the early gastric cancer. CONCLUSION: Taken together, we suggest that loss of Smad4 expression might be associated with the intestinal type of gastric cancer. Also reduced cytoplasmic Smad4 expressions and increased nuclear Smad4 expressions may be associated with the advanced stage of gastric cancer.