IQGAP1 is overexpressed and interacts with ERK in human myeloma cells

AIM:To explore the role of IQ motif-containing GTPase-activating protein 1 (IQGAP1) in the cell proliferation of multiple myeloma and its mechanism. METHODS:RT-PCR and Western blotting were performed to detect the expression of IQGAP1 in human myeloma cell lines RPMI8226 and U266. shRNA-expressing plasmids were used to transfect into RPMI8226 cells to knock down the expression of IQGAP1. MTT assay was used to examine the proliferation of RPMI8226-shIQGAP1 (clone 1) cells, RPMI8226-shRNA negative control cells and un-transfected RPMI8226 cells with or without VEGF/IL-6 treatment. The protein levels of p-ERK1/2, ERK1/2, AKT, p-AKT, STAT3 and p-STAT3 in RPMI8226-shIQGAP1 (clone 1) cells, RPMI8226-shRNA negative control cells and un-transfected RPMI8226 cells were measured by Western blotting. The interaction between IQGAP1 and ERK was determined by the method of co-immunoprecipitation. RESULTS:IQGAP1 was overexpressed in human myeloma cell lines RPMI8226 and U266 as compared with normal lymphocytes. Transfection with shRNA targeting to IQGAP1 decreased the expression levels of IQGAP1 in RPMI8226 cells. The proliferation of RPMI8226 cells decreased when IQGAP1 was knocked down by shRNA with or without VEGF/IL-6 treatment. IQGAP1 affected the proliferation of RPMI8226 cells by regulation of MAP kinase (ERK1/2) pathway. The level of p-ERK1/2 in RPMI8226-shIQGAP1 (clone 1) cells decreased by 70.2% as compared with RPMI8226-shRNA negative control cells and un-transfected RPMI8226 cells. The interaction between IQGAP1 and ERK in RPMI8226 cells was observed. CONCLUSION: IQGAP1 plays an important role in the cell proliferation of multiple myeloma via MAP kinase (ERK) pathway.