Spred2 is involved in imatinib-induced cytotoxicity in chronic myeloid leukemia cells |
| |
Authors: | Xiao-Yun Liu Yue-Feng Yang Chu-Tse Wu Qun-Wei Zhang Qing-Fang Li Hua Wang Li-Sheng Wang |
| |
Affiliation: | a Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China b Lanzhou University of Technology, Lanzhou 730050, PR China |
| |
Abstract: | Spreds, a recently established class of negative regulators of the Ras-ERK (extracellular signal-regulated kinase) pathway, are involved in hematogenesises, allergic disorders and tumourigenesis. However, their role in hematologic neoplasms is largely unknown. Possible effects of Spreds on other signal pathways closely related to Ras-ERK have been poorly investigated. In this study, we investigated the in vitro effects of Spred2 on chronic myeloid leukemia (CML) cells. In addition to inhibiting the well-established Ras-ERK cascade, adenovirus-mediated Spred2 over-expression inhibits constitutive and stem cell factor (SCF)-stimulated sphingosine kinase-1 (SPHK1) and Mcl-1 expression, as well as inhibiting proliferation and inducing apoptosis in CML cells. In K562 cells and primary CML cells, imatinib induces endogenous Spred2 expression. Spred2 silencing by stable RNA interference partly protects K562 cells against imatinib-induced apoptosis. Together, these data implicate Spred2 in imatinib-induced cytotoxicity in CML cells, possibly by inhibiting the Ras-ERK cascade and the pro-survival signaling molecules SPHK1 and Mcl-1. These findings reveal potential targets for selective therapy of CML. |
| |
Keywords: | Spred2 Chronic myeloid leukemia Imatinib Cytotoxicity Sphingosine kinase-1 Mcl-1 |
本文献已被 ScienceDirect 等数据库收录! |
|