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) |