Transcription factor E2F-1 is upregulated in human gastric cancer tissues and its overexpression suppresses gastric tumor cell proliferation.

摘要

The E2F family members play a critical role in cell cycle regulation and other biological processes in the cell. To better understand the involvement of E2F-1 in the development and progression of gastric tumors, we investigated the mutation and expression of E2F-1 in human gastric cancer tissues and the effect of E2F-1 overexpression on the proliferation of gastric carcinoma cells. In this study, 80 pairs of gastric cancer specimens and paratumor tissues from different patients and 40 stomach mucosa specimens from healthy individuals were examined. PCR-SSCP analysis demonstrated that mutations were not detected in any of the gastric cancer and normal tissue specimens. In addition, the results of an immunohistochemistry assay revealed higher expression rates of E2F-1 (P<0.01) in gastric cancer tissues (72.5%) than in paratumor tissues (30.0%) of the same individuals and stomach mucosa from healthy individuals (22.5%). However, no correlation was observed between the E2F-1 levels and patients' clinical features, such as sex, age, histological types, lymph node metastasis, and clinical stages (P>0.05). Finally, the influence of E2F-1 overexpression on the growth of human gastric carcinoma MKN-45 cells in vitro was assessed by measuring colony formation, cell survival, and cell cycle progression. Our data clearly showed that cell growth and proliferation were significantly inhibited in MKN-45 tumor cells transfected with the expression vector encoding E2F-1 in comparison with nontransfected cells or cells transfected with empty vector. These findings suggest that E2F-1, a stable and conservative gene during the oncogenesis and progression of stomach cancers, may potentially serve as a biomarker for clinical diagnosis of gastric carcinomas and as a target for the development of novel therapeutic interventions to treat this disease.