Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells: demonstration of homology to ABC transport genes
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Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells : demonstration of homology to ABC transport genes. / Miyake, K; Mickley, L; Litman, Thomas; Zhan, Z; Robey, R; Cristensen, B; Brangi, M; Greenberger, L; Dean, M; Fojo, T; Bates, S E.
I: Cancer Research, Bind 59, Nr. 1, 01.01.1999, s. 8-13.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells
T2 - demonstration of homology to ABC transport genes
AU - Miyake, K
AU - Mickley, L
AU - Litman, Thomas
AU - Zhan, Z
AU - Robey, R
AU - Cristensen, B
AU - Brangi, M
AU - Greenberger, L
AU - Dean, M
AU - Fojo, T
AU - Bates, S E
N1 - Our discovery of MXR / ABCG2 / BCRP
PY - 1999/1/1
Y1 - 1999/1/1
N2 - Reports of multiple distinct mitoxantrone-resistant sublines without overexpression of P-glycoprotein or the multidrug-resistance associated protein have raised the possibility of the existence of another major transporter conferring drug resistance. In the present study, a cDNA library from mitoxantrone-resistant S1-M1-80 human colon carcinoma cells was screened by differential hybridization. Two cDNAs of different lengths were isolated and designated MXR1 and MXR2. Sequencing revealed a high degree of homology for the cDNAs with Expressed Sequence Tag sequences previously identified as belonging to an ATP binding cassette transporter. Homology to the Drosophila white gene and its homologues was found for the predicted amino acid sequence. Using either cDNA as a probe in a Northern analysis demonstrated high levels of expression in the S1-M1-80 cells and in the human breast cancer subline, MCF-7 AdVp3000. Levels were lower in earlier steps of selection, and in partial revertants. The gene is amplified 10-12-fold in the MCF-7 AdVp3000 cells, but not in the S1-M1-80 cells These studies are consistent with the identification of a new ATP binding cassette transporter, which is overexpressed in mitoxantrone-resistant cells.
AB - Reports of multiple distinct mitoxantrone-resistant sublines without overexpression of P-glycoprotein or the multidrug-resistance associated protein have raised the possibility of the existence of another major transporter conferring drug resistance. In the present study, a cDNA library from mitoxantrone-resistant S1-M1-80 human colon carcinoma cells was screened by differential hybridization. Two cDNAs of different lengths were isolated and designated MXR1 and MXR2. Sequencing revealed a high degree of homology for the cDNAs with Expressed Sequence Tag sequences previously identified as belonging to an ATP binding cassette transporter. Homology to the Drosophila white gene and its homologues was found for the predicted amino acid sequence. Using either cDNA as a probe in a Northern analysis demonstrated high levels of expression in the S1-M1-80 cells and in the human breast cancer subline, MCF-7 AdVp3000. Levels were lower in earlier steps of selection, and in partial revertants. The gene is amplified 10-12-fold in the MCF-7 AdVp3000 cells, but not in the S1-M1-80 cells These studies are consistent with the identification of a new ATP binding cassette transporter, which is overexpressed in mitoxantrone-resistant cells.
KW - ATP-Binding Cassette Transporters
KW - Antineoplastic Agents
KW - Base Sequence
KW - Cloning, Molecular
KW - DNA, Complementary
KW - Drug Resistance, Neoplasm
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Mitoxantrone
KW - Molecular Sequence Data
KW - Sequence Analysis, DNA
KW - Tumor Cells, Cultured
KW - ABCG2
KW - ABCG2/BCRP
KW - MXR
M3 - Journal article
C2 - 9892175
VL - 59
SP - 8
EP - 13
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 1
ER -
ID: 119647556