title: Increased expression of sorcin is associated with multidrug resistance in leukemia cells via up-regulation of MDR1 expression through cAMP response element-binding protein.
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.
authors.affiliation: Department of Biochemistry & Molecular Biology, Division of Biological Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan; Radioisotope Center, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan. Electronic address: yamagisi@mb.kyoto-phu.ac.jp.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamagishi
authors.affiliation: Department of Biochemistry & Molecular Biology, Division of Biological Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Nakao
authors.affiliation: Department of Biochemistry & Molecular Biology, Division of Biological Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Rumi
authors.initials: R
authors.lastname: Kondo
authors.affiliation: Department of Biochemistry & Molecular Biology, Division of Biological Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Nishitsuji
authors.affiliation: Department of Biochemistry & Molecular Biology, Division of Biological Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Youhei
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Biochemistry & Molecular Biology, Division of Biological Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kuga
authors.affiliation: Department of Biochemistry & Molecular Biology, Division of Biological Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Hatayama
authors.affiliation: Department of Biochemistry & Molecular Biology, Division of Biological Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakayama
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D002522:Chlorocebus aethiops; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D019450:Genes, MDR; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C115163:CREB1 protein, human; D002135:Calcium-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C503113:SRI protein, human; D012694:Serine
keywords: CREB; MDR1/P-glycoprotein; Multidrug-resistance; Sorcin