RKIP and 14-3-3ε exert an opposite effect on human gastric cancer cells SGC7901 by regulating the ERK/MAPK pathway differently.
BACKGROUND
Raf-1 kinase inhibitor protein (RKIP) inhibits Raf (a key element in the ERK/MAPK pathway) and is regarded as anti-tumoral. In contrast, 14-3-3 is considered protumoral. However, the pathogenetic role of RKIP and 14-3-3ε in gastric cancer is unclear.


OBJECTIVE
The purpose of this study was to examine the influence of 14-3-3ε and RKIP on SGC7901, the regulation of the ERK/MAKP pathway by both, and the interaction between the two proteins.


METHODS
RKIP and 14-3-3ε genes were introduced into SGC7901 cells using gene cloning technique, then, the bioactivities including the proliferation, migration and invasion of the cells were assessed by MTT and migration assays. ERK/MAKP pathway's activity was examined using real-time quantitative RT-PCR, western blot, immunoprecipitation and 3D-immunolocalization techniques.


RESULTS
Our results showed that RKIP inhibited SGC7901 cells' bioactivities whereas 14-3-3ε upregulated them through the involvement of the ERK/MAPK pathway. RKIP inactivated this pathway, but 14-3-3ε activated it. RKIP and 14-3-3ε were co-localized in the cells and interacted with each other; this attributed to their opposite influence on the ERK/MAPK pathway and the cells bioactivities.


CONCLUSIONS
The ERK/MAPK pathway is involved in the pathogenesis of gastric cancer; RKIP and 14-3-3ε exert an opposite effect on this pathway and the cells possibly via both direct and indirect reactions with the elements in this pathway. The interaction between RKIP and 14-3-3ε may also contribute to their pathogenetic roles in gastric cancer.
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha City, 410008, Hunan Province, People's Republic of China.
Lu
L
Yan
Huan
H
Gu
Jia
J
Li
Meihua
M
Xu
Ting
T
Liu
Yueming
Y
Shen
Bolin
B
Chen
Guiying
G
Zhang
D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology
D048948:14-3-3 Proteins; C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; C482983:YWHAE protein, human