2000 Fiscal Year Final Research Report Summary
ABC Transporters in Cancer and Other Diseases
| Project/Area Number |
11694286
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B).
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | KYUSHU UNIVERSITY |
|---|
Principal Investigator |
KUWANO Michihiko Dept.of Med.Biochemistry, Grad.Sch.of Med.Sciences KYUSHU UNIVERSITY Professor., 大学院・医学研究院, 教授 (80037431)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
UCHIUMI Takeshi Dept.of Med.Biochemistry, Grad.Sch.of Med.Sciences KYUSHU UNIVERSITY Associate Professor, 大学院・医学研究院, 助手 (80253798)
ONO Mayumi Dept.of Med.Biochemistry, Grad.Sch.of Med.Sciences KYUSHU UNIVERSITY Associate Professor, 大学院・医学研究院, 講師 (80128347)
WADA Morimasa Dept.of Med.Biochemistry, Grad.Sch.of Med.Sciences KYUSHU UNIVERSITY Associate Professor, 大学院・医学研究院, 助教授 (20220965)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Keywords | anticancer agents / MRP / MDR1 / efflux pump / cMOAT / MRP2 / YB-1 / Dubin-Johnson syndrome / DNA methylation |
|---|
| Research Abstract |
The appearance of tumor cells resistant to multiple anticancer agents poses a serious problem during treatment of cancer patients using chemotherapeutic agents. The acquisition of such a multidrug resistance phenotype in cancer cells is often associated with increased expression of cell surface P-glycoprotein(P-gp) encoded by the multidrug resistance 1 (MDR1) gene that functions as a drug efflux pump, and thereby reduces the intracellular concentration of drugs. However, non-P-gp-mediated multidrug resistance is also frequently observed. In the present study, we identified and determined the nucleotide sequence of the cMOAT/MRP2 and MRP3 genes. We then found the participation of the genes on the drug resistance to vincristine, cisplatin, doxorubicin and methotrexate, and etoposide and methotrexate, respectively, by transfection experiment of the cDNAs. We also found that the overexpression of the MDR1 gene in cancer cells was trigared by different mechanisms such as CpG de-methylation, Alu-mediated gene rearrangement and translocation of the transcrptional factor YB-1 among different cancer type. Besides the multidrug resistance, these ATP binding cassette (ABC) transporters have important phisiological functions. We identified four mutations in cMOAT/MRP2 gene in Dubin-Johnson syndrome, human conjugated hyperbilirubinemia, suggesting the function of the cMOAT/MRP2 gene in the transfer of endogenous and exogenous anionic conjugates from hepatocytes into the bile.
|
-
-
-
-
-
-
[Publications] Nagayama, J., Iino, M., Tada, Y., Kusaba, H., Kiue, A., Ohsima, K., Kuwano, M.and Wada, M.: "Retrovirus insertion and transcriptional activation of the multidrug resistance (mdrl α) gene in leukemias treated by a chemotherapeutic agent in vivo."Blood. 97. 759-766 (2001)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Okamoto, T., Izumi, H., Imamura, T., Takano, H., Ise, T, Uchiumi, T., Kuwano, M.and Kohno, K.: "Direct interaction of p53 with the Y-box binding protein, YB-1 : a mechanism for regulation of human gene expression."Oncogene. 19. 6194-6202 (2000)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Harada, T., Nishie, A., Torigoe, K., Ikezaki, K., Shono, T., Maehara, Y., Kuwano, M.and Wada, M.: "The specific expression of three novel splice variant forms of human metalloprotease-like disintegrin-like cysteine-rich protein 2 gene in brain tissues and gliomas."Jpn.J.Cancer Res.. 91. 1001-1006 (2000)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Tada, Y., Wada, M., Kuroiwa, K., Harada, T., Tsuneyoshi, M., Nakagawa, M., Naito, S., Kuwano, M.: "MDR1 overexpression and altered degree of methylation at the promoter region in bladder cancer during chemotherapeutic treatment."Clinical Cancer Res.. 6. 4618-4627 (2000)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Hinoshita, E., Uchiumi, T., Taguchi, K., Kinukawa, N., Tsuneyoshi, M., Maehara, Y., Sugimachi, K.and Kuwano, M.: "Increased expression of an ATP-binding cassette superfamily transporter, multidrug resistance protein 2, in human colorectal carcinomas."Clinical Cancer Res.. 6. 2401-2407 (2000)
Description
「研究成果報告書概要(欧文)」より
