Involvement of the multidrug resistance protein 3 in drug sensitivity and its expression in human glioma

Sei Haga, Eiji Hinoshita, Kiyonobu Ikezaki, Masashi Fukui, George L. Scheffer, Takeshi Uchiumi, Michihiko Kuwano

Research output: Contribution to journalArticle

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Abstract

The multidrug resistance protein (MRP) family belongs to the ATP-binding cassette superfamily (ABC) of transporters, which are involved in ATP-dependent transport of hydrophobic compounds. One of the MRP family, MRP1, is partially associated with the multidrug resistance phenotype in brain tumors. In this study, we asked whether another MRP family gene, MRP3, could affect drug sensitivity to anticancer agents in human glioma cell lines and clinical glioma specimens. We first produced two antisense transfectants by introduction of antisense MRP3 cDNA into the glioma cell line NHG2, which endogenously expresses MRP3. The two MRP3 antisense transfectants showed 2- to 5-fold increases in drug sensitivity to etoposide and cisplatin compared with NHG2 cells, but their sensitivity to vincristine or nitrosourea was not changed. Two MRP3 cDNA sense transfectants of pig kidney cell lines showed 4- to 6-fold drug resistance to etoposide, but only 1.4- to 1.5-fold to cisplatin. We next compared the mRNA levels of four ABC transporters, multidrug resistance 1 (MDR1), MRP1, MRP2 and MRP3 in clinical samples, including 34 patients with gliomas, by quantitative RT-PCR analysis. In some of the clinical samples, increased expression of MRP1 and MRP3 was apparent in malignant gliomas. In situ hybridization revealed that glioma cells were stained with MRP3 probe. MRP3 may modulate drug sensitivity to certain anticancer agents in human gliomas.

Original languageEnglish
Pages (from-to)211-219
Number of pages9
JournalJapanese Journal of Cancer Research
Volume92
Issue number2
DOIs
Publication statusPublished - Feb 2001

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Glioma
P-Glycoproteins
Pharmaceutical Preparations
ATP-Binding Cassette Transporters
Multiple Drug Resistance
Etoposide
Cell Line
Antineoplastic Agents
Cisplatin
Complementary DNA
Vincristine
multidrug resistance protein 3
Drug Resistance
Brain Neoplasms
In Situ Hybridization
Swine
Adenosine Triphosphate
Phenotype
Kidney
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Involvement of the multidrug resistance protein 3 in drug sensitivity and its expression in human glioma. / Haga, Sei; Hinoshita, Eiji; Ikezaki, Kiyonobu; Fukui, Masashi; Scheffer, George L.; Uchiumi, Takeshi; Kuwano, Michihiko.

In: Japanese Journal of Cancer Research, Vol. 92, No. 2, 02.2001, p. 211-219.

Research output: Contribution to journalArticle

Haga, Sei ; Hinoshita, Eiji ; Ikezaki, Kiyonobu ; Fukui, Masashi ; Scheffer, George L. ; Uchiumi, Takeshi ; Kuwano, Michihiko. / Involvement of the multidrug resistance protein 3 in drug sensitivity and its expression in human glioma. In: Japanese Journal of Cancer Research. 2001 ; Vol. 92, No. 2. pp. 211-219.
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