Expression and significance of HERG protein in gastric cancer.
OBJECTIVE
Our previous studies showed that delayed rectifier potassium currents existed in human gastric cancer cells and the currents were related to the growth of gastric cancer cells. Human ether-a-go-go-related gene (herg) encoding alpha subunit of delayed rectifier potassium channel has been indicated with involvement in tumor cell growth and death. The purpose of the present study is to investigate the expression of HERG protein in gastric cancer tissue and cells; analyze the relationship between the expression of HERG protein and the clinicopathological characteristics of patients with gastric cancer; explore the effects of HERG protein on biological behaviours of gastric cancer cells.


METHODS
The expression of HERG protein in gastric cancer tissues and cells was measured by immunohistochemistry and Western blot, respectively. Reduction of HERG protein was carried out by siRNA technology. The proliferation, ability of clone formation, cell cycle, apoptosis and invasive ability of gastric cancer cells were evaluated by MTT assay, clone formation assay, flow cytometry and cell invasion assay. Tumor growth in nude mice was to be used to access the tumorigenicity of gastric cancer cells and HERG currents were recorded by patch-clamp.


RESULTS
HERG protein was exclusively expressed in gastric cancer cells. The expression of HERG protein was associated with tumor differentiation, TNM stage and lymph node involvement of gastric cancer. Silencing HERG protein could eliminate the HERG currents and inhibit proliferation, clone formation, invasiveness and tumorigenicity of gastric cancer cells. Reducing HERG protein could also inhibit gastric cancer cells entering S phase from G(1) phase and induce apoptosis of gastric cancer cells.


CONCLUSIONS
HERG protein is involved in carcinogenesis of gastric cancer and is a potential therapeutic target of gastric cancer.
Shao
Xiao-Dong
XD
Department of Gastroenterology, Shenyang General Hospital, Shenyang, China. sxdsys608@sohu.com
Wu
Kai-Chun
KC
Guo
Xiao-Zhong
XZ
Xie
Man-Jiang
MJ
Zhang
Jing
J
Fan
Dai-Ming
DM
D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000473:pathology
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human