title: Regulations of ABCB1 and ABCG2 expression through MAPK pathways in acute lymphoblastic leukemia cell lines.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  The expressions of ABCB1 and ABCG2 genes were regulated through MAPK/ERK and JNK pathways in the human ALL cell lines.
authors: Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan atsuji@mail.ecc.u-tokyo.ac.jp.
authors: Hirotaka
authors: H
authors: Tomiyasu
authors: Manabu
authors: M
authors: Watanabe
authors: Kanji
authors: K
authors: Sugita
authors: Yuko
authors: Y
authors: Goto-Koshino
authors: Yasuhito
authors: Y
authors: Fujino
authors: Koichi
authors: K
authors: Ohno
authors: Sumio
authors: S
authors: Sugano
authors: Hajime
authors: H
authors: Tsujimoto
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020112:Rhodamine 123 / Q000378:metabolism; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics; D000099187:Major Vault Protein
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D017931:DNA Primers; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D020112:Rhodamine 123; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; C421109:multidrug resistance-associated protein 1
keywords: ABCG2; ALL; BCRP; MAPK; multidrug resistance