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Published on: February 5, 2018
The roles of REIC gene and its encoding product in gastric carcinoma
1Department of Pathophysiology, Institute of Pathology and Pathophysiology, College of Basic Medicine, China Medical University, Shenyang, China.
Abstract:
REIC is downregulated in immortalized cell lines compared with the parental normal counterparts. It may inhibit colony formation, tumor growth and induce apoptosis. Here, gastric carcinoma or epithelial cells transfected with REIC-expressing plasmid, its siRNA or treated with recombinant REIC were subjected to the phenotypes' measurement or related molecules' detection. REIC expression was examined in gastric carcinomas by RT-PCR, western blot and immunohistochemistry. REIC overexpression or treatment resulted in a low karyoplasmic ratio and proliferation, G₁ arrest, high apoptosis, low migration, invasion or lamellipodia formation in AGS cells. REIC knockdown caused the opposite in GES-1 cells. Anti-REIC antibody blocked the effects of REIC overexpression on proliferation, G₁/S progression and apoptosis. Ectopic REIC expression downregulated the expression of β-catenin, phosphorylated S6K (Thr389), phosphorylated Akt1/2/3 (Ser473), cyclin D2 and E, WAVE2 and upregulated phosphorylated mTOR (Ser2448) expression and the mRNA level of Akt1, Akt2, mTOR, Raptor and Rictor in AGS cells. REIC expression was negatively associated with tumor size, lymph node metastasis, dedifferentiation or poor prognosis of carcinoma. The serum REIC level was significantly higher in healthy individuals than the carcinoma patients and inversely linked to tumor size by ELISA. The possible mechanisms underlying the forced REIC overexpression or recombinant REIC mediated the reversal of the aggressive phenotypes of gastric carcinoma cells are to downregulate β-catenin and WAVE2 expression and to alter other related target proteins. Downregulated REIC expression was closely linked to aggressive behaviors and poor prognosis of gastric carcinoma.
Insights
Reduced REIC protein expression correlates with aggressive gastric cancer and poor prognosis. REIC (Reduced Expression in Immortalized Cells) may inhibit tumor growth and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Reduced Expression in Immortalized Cells (REIC) is downregulated in cancer cells compared to normal cells.
- REIC may play a role in inhibiting tumor growth, colony formation, and inducing apoptosis.
Purpose of the Study:
- To investigate the role of REIC in gastric carcinoma.
- To examine the association between REIC expression and clinicopathological features and prognosis of gastric cancer.
- To elucidate the molecular mechanisms underlying REIC's function in gastric cancer cells.
Main Methods:
- Gastric carcinoma and epithelial cells were transfected with REIC-expressing plasmids or siRNA, or treated with recombinant REIC.
- REIC expression was analyzed using RT-PCR, Western blot, and immunohistochemistry.
- Cell phenotypes (proliferation, apoptosis, migration, invasion) and molecular markers were measured.
Main Results:
- REIC overexpression inhibited proliferation, migration, and invasion, while promoting apoptosis in AGS gastric cancer cells.
- REIC knockdown in GES-1 cells induced opposite effects.
- REIC expression was negatively associated with tumor size, lymph node metastasis, and poor prognosis in gastric carcinoma patients.
- Serum REIC levels were lower in gastric cancer patients and inversely correlated with tumor size.
Conclusions:
- Downregulated REIC expression is linked to aggressive gastric carcinoma behaviors and poor prognosis.
- REIC overexpression reverses aggressive phenotypes by downregulating β-catenin and WAVE2, and altering other target proteins.
- REIC serves as a potential therapeutic target and prognostic biomarker for gastric cancer.
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