Regulations of ABCB1 and ABCG2 expression through MAPK pathways in acute lymphoblastic leukemia cell lines

Hirotaka Tomiyasu; Manabu Watanabe; Kanji Sugita; Yuko Goto-Koshino; Yasuhito Fujino; Koichi Ohno; Sumio Sugano; Hajime Tsujimoto

Regulations of ABCB1 and ABCG2 expression through MAPK pathways in acute lymphoblastic leukemia cell lines

Anticancer Res. 2013 Dec;33(12):5317-23.

Authors

Hirotaka Tomiyasu¹, Manabu Watanabe, Kanji Sugita, Yuko Goto-Koshino, Yasuhito Fujino, Koichi Ohno, Sumio Sugano, Hajime Tsujimoto

Affiliation

¹ 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 [email protected].

PMID: 24324065

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.

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.

Keywords: ABCG2; ALL; BCRP; MAPK; multidrug resistance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters / genetics*
Base Sequence
Cell Line, Tumor
DNA Primers
Gene Expression Regulation, Neoplastic*
Humans
MAP Kinase Signaling System*
Multidrug Resistance-Associated Proteins / genetics
Neoplasm Proteins / genetics*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Rhodamine 123 / metabolism
Vault Ribonucleoprotein Particles / genetics

Substances

ABCB1 protein, human
ABCG2 protein, human
ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters
DNA Primers
Multidrug Resistance-Associated Proteins
Neoplasm Proteins
RNA, Messenger
Vault Ribonucleoprotein Particles
major vault protein
Rhodamine 123
multidrug resistance-associated protein 1