Objective： Chronic lymphocytic leukemia （CLL） and mantle cell lymphoma （MCL） cells over-express a guanine exchange factor （GEF）, Rasgrf-1. This GEF increases active Ras as it catalyzes the removal of GDP from R...Objective： Chronic lymphocytic leukemia （CLL） and mantle cell lymphoma （MCL） cells over-express a guanine exchange factor （GEF）, Rasgrf-1. This GEF increases active Ras as it catalyzes the removal of GDP from Ras so that GTP can bind and activate Ras. This study aims to study the mechanism of action of Rasgrf-1 in B-cell malignancies. Methods： N-terminus truncated Rasgrf-1 variants have a higher GEF activity as compared to the full-length transcript therefore a MCL cell line with stable over-expression of truncated Rasgrf-1 was established. The B-cell receptor （BCR） and chemokine signaling pathways were compared in the Rasgrf-I over-expressing and a control transfected cell line. Results： Cells over-expressing truncated form of Rasgrf-1 have a higher proliferative rate as compared to control transfected cells. BCR was activated by lower concentrations of anti-IgM antibody in Rasgrf-1 over-expressing cells as compared to control cells indicating that these cells are more sensitive to BCR signaling. BCR signaling also phosphorylates Rasgrf-1 that further increases its GEF function and amplifies BCR signaling. This activation of Rasgrf-1 in over-expressing cells resulted in a higher expression of phospho-ERK, AKT, BTK and PKC-alpha as compared to control cells. Besides BCR, Rasgrf-1 over-expressing cells were also more sensitive to microenvironment stimuli as determined by resistance to apoptosis, chemotaxis and ERK pathway activation. Conclusions： This GEF protein sensitizes B-cells to BCR and chemokine mediated signaling and also upregulates a number of other signaling pathways which promotes growth and survival of these cells.展开更多
t Objective： The aim of our study was to investigate the expression of guanine nucleotide exchange factor Dock180 in ovarian tumor, and its significance in the initiation and progression of ovarian cancer. Methods： ...t Objective： The aim of our study was to investigate the expression of guanine nucleotide exchange factor Dock180 in ovarian tumor, and its significance in the initiation and progression of ovarian cancer. Methods： Immunohistochemical staining with SP method was conducted to identify the expression of Dock180 protein in epithelial ovarian tumor in 68 cases. Results： Dock180 present with higher expression in ovarian cancer, as compared with than that in low malignant tumor and benign ovarian tumor （P 〈 0,01）, In ovarian cancer, Dock180 expression was increased with the increased FIGO stage and grade. Conclusion： Dock180 overexpression may play an important role in the development and progression of ovarian cancer and it could be used as a new measurement of malignant biological behavior of ovarian cancer.展开更多
文摘Objective： Chronic lymphocytic leukemia （CLL） and mantle cell lymphoma （MCL） cells over-express a guanine exchange factor （GEF）, Rasgrf-1. This GEF increases active Ras as it catalyzes the removal of GDP from Ras so that GTP can bind and activate Ras. This study aims to study the mechanism of action of Rasgrf-1 in B-cell malignancies. Methods： N-terminus truncated Rasgrf-1 variants have a higher GEF activity as compared to the full-length transcript therefore a MCL cell line with stable over-expression of truncated Rasgrf-1 was established. The B-cell receptor （BCR） and chemokine signaling pathways were compared in the Rasgrf-I over-expressing and a control transfected cell line. Results： Cells over-expressing truncated form of Rasgrf-1 have a higher proliferative rate as compared to control transfected cells. BCR was activated by lower concentrations of anti-IgM antibody in Rasgrf-1 over-expressing cells as compared to control cells indicating that these cells are more sensitive to BCR signaling. BCR signaling also phosphorylates Rasgrf-1 that further increases its GEF function and amplifies BCR signaling. This activation of Rasgrf-1 in over-expressing cells resulted in a higher expression of phospho-ERK, AKT, BTK and PKC-alpha as compared to control cells. Besides BCR, Rasgrf-1 over-expressing cells were also more sensitive to microenvironment stimuli as determined by resistance to apoptosis, chemotaxis and ERK pathway activation. Conclusions： This GEF protein sensitizes B-cells to BCR and chemokine mediated signaling and also upregulates a number of other signaling pathways which promotes growth and survival of these cells.
基金Supported by grants from the National Natural Science Foundation of China (No. C30772330)the Natural Science Foundation Project of Chongqing (No. 2010BB5387)partly by the Chongqing Municipal Health Bureau Foundation Project (No. 2010-2-062)
文摘t Objective： The aim of our study was to investigate the expression of guanine nucleotide exchange factor Dock180 in ovarian tumor, and its significance in the initiation and progression of ovarian cancer. Methods： Immunohistochemical staining with SP method was conducted to identify the expression of Dock180 protein in epithelial ovarian tumor in 68 cases. Results： Dock180 present with higher expression in ovarian cancer, as compared with than that in low malignant tumor and benign ovarian tumor （P 〈 0,01）, In ovarian cancer, Dock180 expression was increased with the increased FIGO stage and grade. Conclusion： Dock180 overexpression may play an important role in the development and progression of ovarian cancer and it could be used as a new measurement of malignant biological behavior of ovarian cancer.
