Associations between mutations of the cell cycle checkpoint kinase 2 gene and gastric carcinogenesis

Abstract

Gastric cancer is the most common malignant tumor of the digestive system. The etiology of gastric cancer is complex, and susceptibility at the genetic level remains to be fully elucidated in genetic investigations. In the present study, mutations of the cell cycle checkpoint kinase 2 (CHEK2) gene and its association with gastric cancer were examined. Reverse transcription‑quantitative polymerase chain reaction technology was used to detect the expression of CHEK2 and it was found that the expression of CHEK2 was low in gastric cancer. Using sequencing analysis, it was found that the low expression level of CHEK2 was associated with expression of its mutation. The present study also established a CHEK2‑overexpressing mutant and confirmed that CHEK2 promoted gastric cancer cell proliferation. Overexpression of the CHEK2 mutation was confirmed to promote cancer cell migration and invasion. Furthermore, western blot analysis results revealed that overexpression of the CHEK2 mutation downregulated E‑cadherin and upregulated vimentin expression, indicating the mechanism underlying the altered biological behavior. These results suggested that there was a correlation between mutation of the CHEK2 gene and gastric cancer, and provided an experimental basis for antitumor drug investigation and development according to its mutation target.

High FAM189B Expression and Its Prognostic Value in Patients with Gastric Cancer

“…In this study, we also showed the clinical significance of two hub genes (CHEK2 and PLK1) in the cell cycle pathway and their correlations with FAM189B. Both of these two coexpressed genes of FAM189B have been well reported to play essential roles in the cell cycle regulation and development of GC [30][31][32][33][34]. Although there was only preliminary evidence of a correlation, this finding also suggests that FAM189B may affect the clinical progression of GC by disturbing the cell cycle of GC cells.…”

Recurrent Germline Mutations of CHEK2 as a New Susceptibility Gene in Patients with Pheochromocytomas and Paragangliomas

“…Though in PPGLs, the function of CHEK2 gene has not been well characterized; however, CHEK2 role in cell proliferation and tumor suppression has been confirmed by various reports. Hong et al established a CHEK2-1100delC mutant, which promoted the gastric cancer cell proliferation, migration, and invasion, with downregulation of E-cadherin and upregulated vimentin expression, suggesting its possible role in altered biological behavior as epithelial mesenchymal transition (EMT) [ 21 ]. Another study reported the novel recurrent CHEK2-Y390 C mutant associated with increased breast cancer risk in Chinese population.…”