BACKGROUND: One of the major causes of failure in chemotherapy for patients with acute lymphoblastic leukemia (ALL) is the acquisition of multidrug resistance (MDR). Predominant mechanisms for MDR acquisition include the overexpression of efflux pumps. In the present study, the regulation of the expression of two genes that encode efflux pumps, ATP-binding cassette, sub-family B, member 1 (ABCB1) and ABCG2, through mitogen-activated protein kinase (MAPK) pathways was examined. MATERIALS AND METHODS: ABCB1 and ABCG2 mRNAs were quantified in a T-ALL cell line, CCRF-HSB-2 and a B-ALL cell line, YAMN90 using real-time RT-PCR. Changes in the mRNA amounts of these genes were examined after activation or inhibition of MAPK/extracellular signal-regulated kinase (ERK) pathway and c-Jun NH2-terminal kinase (JNK) pathway. RESULTS: Activation of MAPK/ERK pathway up-regulated ABCB1 expression but down-regulated ABCG2 expression. Activation of JNK pathway up-regulated ABCG2 gene expression. CONCLUSION: The expressions of ABCB1 and ABCG2 genes were regulated through MAPK/ERK and JNK pathways in the human ALL cell lines.
BACKGROUND: One of the major causes of failure in chemotherapy for patients with acute lymphoblastic leukemia (ALL) is the acquisition of multidrug resistance (MDR). Predominant mechanisms for MDR acquisition include the overexpression of efflux pumps. In the present study, the regulation of the expression of two genes that encode efflux pumps, ATP-binding cassette, sub-family B, member 1 (ABCB1) and ABCG2, through mitogen-activated protein kinase (MAPK) pathways was examined. MATERIALS AND METHODS:ABCB1 and ABCG2 mRNAs were quantified in a T-ALL cell line, CCRF-HSB-2 and a B-ALL cell line, YAMN90 using real-time RT-PCR. Changes in the mRNA amounts of these genes were examined after activation or inhibition of MAPK/extracellular signal-regulated kinase (ERK) pathway and c-Jun NH2-terminal kinase (JNK) pathway. RESULTS: Activation of MAPK/ERK pathway up-regulated ABCB1 expression but down-regulated ABCG2 expression. Activation of JNK pathway up-regulated ABCG2 gene expression. CONCLUSION: The expressions of ABCB1 and ABCG2 genes were regulated through MAPK/ERK and JNK pathways in the human ALL cell lines.
Authors: Anyan Xie; René J Robles; Samiran Mukherjee; Haohai Zhang; Linda Feldbrügge; Eva Csizmadia; Yan Wu; Keiichi Enjyoji; Alan C Moss; Leo E Otterbein; Francisco J Quintana; Simon C Robson; Maria Serena Longhi Journal: J Autoimmun Date: 2018-08-08 Impact factor: 7.094