RRC ID 45056
著者 Yamagishi N, Nakao R, Kondo R, Nishitsuji M, Saito Y, Kuga T, Hatayama T, Nakayama Y.
タイトル Increased expression of sorcin is associated with multidrug resistance in leukemia cells via up-regulation of MDR1 expression through cAMP response element-binding protein.
ジャーナル Biochem Biophys Res Commun
Abstract Sorcin, a 22 kDa Ca(2+) binding protein, was first identified in a vincristine-resistant Chinese hamster lung cell line, and was later demonstrated to be involved in the development of multidrug-resistance (MDR) phenotypes in a variety of human cancer cell lines. However, the exact role of sorcin in MDR cells is yet to be fully elucidated. Here we explored the role of sorcin in the development of MDR in leukemia cells, and revealed that the expression level of sorcin was directly correlated to the expression of MDR1/P-glycoprotein (P-gp). In addition, it was shown that sorcin induced the expression of MDR1/P-gp through a cAMP response element (CRE) between -716 and -709 bp of the mdr1/p-gp gene. Furthermore, overexpression of sorcin increased the phosphorylation of CREB1 and the binding of CREB1 to the CRE sequence of mdr1/p-gp promoter, and induced the expression of MDR1/P-gp. These findings suggested that sorcin induces MDR1/P-gp expression markedly through activation of the CREB pathway and is associated with the MDR phenotype. The new findings may be helpful for understanding the mechanisms of MDR in human cancer cells, prompting its further investigation as a molecular target to overcome MDR.
巻・号 448(4)
ページ 430-6
公開日 2014-6-13
DOI 10.1016/j.bbrc.2014.04.125
PII S0006-291X(14)00788-8
PMID 24796664
MeSH ATP Binding Cassette Transporter, Subfamily B ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics* ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism* Animals Binding Sites / genetics COS Cells Calcium-Binding Proteins / antagonists & inhibitors Calcium-Binding Proteins / genetics* Calcium-Binding Proteins / metabolism* Chlorocebus aethiops Cyclic AMP Response Element-Binding Protein / chemistry Cyclic AMP Response Element-Binding Protein / genetics Cyclic AMP Response Element-Binding Protein / metabolism* Drug Resistance, Multiple / genetics Drug Resistance, Neoplasm / genetics Genes, MDR Humans K562 Cells Leukemia / drug therapy Leukemia / genetics* Leukemia / metabolism* Phosphorylation Promoter Regions, Genetic RNA, Small Interfering / genetics Recombinant Proteins / genetics Recombinant Proteins / metabolism Serine / chemistry Signal Transduction Transcription, Genetic Up-Regulation
IF 2.985
引用数 20
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 K562/Adr(RCB1898) K562/Vin(RCB2111) K562(RCB1897) COS-7(RCB0539)