Vav1, as a key downstream signaling molecule of T cell receptor, includes a catalytic core DH-PH-ZF domain with the function as guanine nucleotide exchange factor (GEF), and a SH3-SH2-SH3 domain with the function as adaptor protein. These two structures of Vav1 play different roles in the development, activation, proliferation and function of T cells, and thereby exert the different regulatory effect on the occurrence and development of autoimmune disease, graft rejection, cancer and other clinical conditions, implicating that Vav1 might be a potential therapeutic target for these diseases. This paper reviews the role of Vav1 in T cells and the occurrence of related diseases.
Adaptor Proteins, Signal Transducing ; Animals ; Autoimmune Diseases ; genetics ; physiopathology ; Humans ; Neoplasms ; genetics ; physiopathology ; Proto-Oncogene Proteins c-vav ; chemistry ; immunology ; metabolism ; T-Lymphocytes

OBJECTIVEThe purpose of this study was to investigate the effect and mechanism of Vav3 gene on the proliferation of human gastric cancer cell line SGC7901.

METHODSThe expressions of Vav3 proten in gastric cancer tissue, tumor-adjacent tissue, human gastric cancer cell line SGC7901 and gastric epithelial cell line GES-1 cells were tested by Western blot. Vav3-siRNA was transfected into the SGC7901 cells. The proliferation of SGC7901 cells in vitro was measured by MTT assay. Cell cycle of SGC7901 cells was determined by flow cytometry.The expressions of proliferation-related genes PCNA, p16, cyclin D1, Rb were determined by qPCR and Western blot assay. Orthotopic transplantation nude mouse models of gastric cancer were prepared, and the tumor growth and expressions of PCNA, P16, cyclin D1, and Rb proteins were examined.

RESULTSThe relative expressions of Vav3 in the gastric cancer and peritumoral tissue were 0.910±0.242 and 0.243±0.045, respectively; the relative expressions of Vav3 in SGC7901 and GSE-1 cells were 0.925±0.127 and 0.277±0.038, respevtively (both P<0.05). The expression of Vav3 protein in SGC7901 cells was effectively inhibited by Vav3-siRNA. Proliferation of SGC7901 cells was inhibited by (83.43±10.17)% after 80 nmol/L Vav3-siRNA transfection (P<0.05). The ratio of SGC7901 cells in G0/G1 phase was increased, and in S phase decreased after Vav3-siRNA transfection (both P<0.05). The expressions of PCNA and cyclin D1 were decreased in cells after Vav3-siRNA transfection, and expressions of p16 and Rb were increased after Vav3-siRNA transfection (P<0.05 for all). The tumor growth in the Vav3-siRNA group was much slower than that in the other 2 control groups of nude mouse models. Compared with the two control groups, expressions of PCNA and cyclin D1 were significantly lower in the Vav3-siRNA group, while expressions of p16 and Rb were increased (P<0.05 for all).

CONCLUSIONVav3 can promote the proliferation of gastric cancer cells by regulating proliferation-related genes.

Animals ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Cyclin D1 ; metabolism ; Humans ; Mice ; Mice, Nude ; Proto-Oncogene Proteins c-vav ; metabolism ; RNA, Small Interfering ; Stomach Neoplasms ; metabolism ; Transfection