| Project/Area Number |
18591429
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Gunma University |
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Principal Investigator |
KOIBUCHI Yukio Gunma University, FACULTY OF MEDICINE, ASSISTANT PROFESSOR (10323346)
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| Co-Investigator(Kenkyū-buntansha) |
HORIGUCHI Jun GUNMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR (70272242)
ROKUTANDA Nana GUNMA UNIVERSITY, GRADUATE FACULTY OF MEDICINE, POST GRADUATE (50420097)
IWASAKI Toshiharu GUNMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSISTANT PROFESSOR (80375576)
KOIBUCHI Noriyuki GUNMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR (80234681)
IINO Yuichi GUNMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR (50124649)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,860,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | PCB / SXR / breast cancer / transcription / ERα / coactivator / corepressor / CYP3A4 / ER / PR / UGT / 乳がん / 乳癌 / 薬剤代謝 / グルクロン酸抱合 |
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| Research Abstract |
Polychlorinated biphenyls (PCBs) have been known as environmental chemicals that cause various effects on endocrine system and speculated the association with the production of carcinomas. Using reporter gene assays, we showed that PCB augmented the SXR-mediated transcription in MCF-7 breast cancer cells but not in CV-1 cells. On the other hand, in the presence of rifampicin, agonist of SXR, PCB augmented the transcription effectively at 10^<-11> M in CV-1 cells, but not in MCF-7 cells. ERα did not affect the transcription through SXRE in CV-1 cells. Cofactors including SRC-1, p/CIP, N-CoR and SMRT slightly altered bindings to SXR using a series of mammalian two-hybrid assays. These results indicate that the sum of subtle alterations of cofactor-SXR bindings by PCB may result in disruption of SXR-mediated transcription. In summary, SXR-mediated transcription induced by PCBs may result in disruption of local drug metabolism, in addition to native endocrine systems.
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