Increased expression of an ATP-binding cassette superfamily transporter, multidrug resistance protein 2, in human colorectal carcinomas

Eiji Hinoshita, Takeshi Uchiumi, Ken Ichi Taguchi, Naoko Kinukawa, Masazumi Tsuneyoshi, Yoshihiko Maehara, Keizo Sugimachi, Michihiko Kuwano

Research output: Contribution to journalArticle

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Abstract

The expression of ATP-binding cassette superfamily transporter genes, such as P-glycoprotein/multidrug resistance (MDR) 1 and MDR protein (MRP) 1, is often upregulated in various tumor types and is involved in responses to some anticancer chemotherapeutic agents. Five human MRP subfamily members (MRP2-6) with structural similarities to MRP1 have been identified. The relationships between MRP2-6 mRNA levels and drug resistance are not well understood. Data on 45 patients with colorectal cancer were analyzed. Of the ATP-binding cassette superfamily genes, we asked whether mRNA levels of MDR1, MRP1, MRP2, and MRP3 correlated with drug resistance to anticancer agents. For this analysis, we used quantitative reverse transcription-PCR, and the sensitivity to anticancer agents in surgically resected colon carcinomas was determined using the in vitro succinate dehydrogenase inhibition test. MDR1, MRP1, and MRP3 were highly expressed in normal colorectal mucosa, and the relative mRNA levels of MDR1, MRP1, and MRP3 in cancerous tissues compared with noncancerous tissues were decreased or unchanged. By contrast, MRP2 mRNA expression was low in normal colorectal mucosa and specifically increased in cancer regions compared with noncancerous regions. Of the anticancer agents prescribed for patients with colorectal cancers, including doxorubicin, mitomycin C, cisplatin, 5-fluorouracil, etoposide, and a camptothecin derivative, mRNA expression of MRP2 was significantly associated with resistance to cisplatin. MRP2 may be important for resistance to cisplatin treatment in colorectal cancer.

Original languageEnglish
Pages (from-to)2401-2407
Number of pages7
JournalClinical Cancer Research
Volume6
Issue number6
Publication statusPublished - Jun 1 2000

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ATP-Binding Cassette Transporters
Colorectal Neoplasms
Antineoplastic Agents
Messenger RNA
Cisplatin
Drug Resistance
Mucous Membrane
Camptothecin
Succinate Dehydrogenase
Multiple Drug Resistance
P-Glycoprotein
Mitomycin
Etoposide
Fluorouracil
Doxorubicin
Genes
Reverse Transcription
Neoplasms
Colon
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Hinoshita, E., Uchiumi, T., Taguchi, K. I., Kinukawa, N., Tsuneyoshi, M., Maehara, Y., ... Kuwano, M. (2000). Increased expression of an ATP-binding cassette superfamily transporter, multidrug resistance protein 2, in human colorectal carcinomas. Clinical Cancer Research, 6(6), 2401-2407.

Increased expression of an ATP-binding cassette superfamily transporter, multidrug resistance protein 2, in human colorectal carcinomas. / Hinoshita, Eiji; Uchiumi, Takeshi; Taguchi, Ken Ichi; Kinukawa, Naoko; Tsuneyoshi, Masazumi; Maehara, Yoshihiko; Sugimachi, Keizo; Kuwano, Michihiko.

In: Clinical Cancer Research, Vol. 6, No. 6, 01.06.2000, p. 2401-2407.

Research output: Contribution to journalArticle

Hinoshita, E, Uchiumi, T, Taguchi, KI, Kinukawa, N, Tsuneyoshi, M, Maehara, Y, Sugimachi, K & Kuwano, M 2000, 'Increased expression of an ATP-binding cassette superfamily transporter, multidrug resistance protein 2, in human colorectal carcinomas', Clinical Cancer Research, vol. 6, no. 6, pp. 2401-2407.
Hinoshita, Eiji ; Uchiumi, Takeshi ; Taguchi, Ken Ichi ; Kinukawa, Naoko ; Tsuneyoshi, Masazumi ; Maehara, Yoshihiko ; Sugimachi, Keizo ; Kuwano, Michihiko. / Increased expression of an ATP-binding cassette superfamily transporter, multidrug resistance protein 2, in human colorectal carcinomas. In: Clinical Cancer Research. 2000 ; Vol. 6, No. 6. pp. 2401-2407.
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