1996 Fiscal Year Final Research Report Summary
Regulators on expression of genes associated with anticancer drug resistance
| Project/Area Number |
07807021
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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 |
Human pathology
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| Research Institution | Fukushima Medical University School of Medicine (1996)
Niigata University (1995) |
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Principal Investigator |
FUKUDA Takeaki Fukushima medical university school of Medicine, Second department of Pathology, Associate professor., 医学部・病理, 助教授 (20199235)
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| Co-Investigator(Kenkyū-buntansha) |
KISHI Kenji Niigata University Hospital, Assistant professor., 医学部・附属病院, 講師 (30186209)
KAKIHARA Toshio Niigata University School of Medicine, Department of Pediatrics., 医学部・小児科, 助手 (70262433)
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| Project Period (FY) |
1995 – 1996
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| Keywords | 抗癌剤耐性 / 核内因子 / NF-κB / 熱ショック蛋白 / AP-1 |
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| Research Abstract |
There are few reports on the regulation of the expression of the genes associated with resistance of the anticancer drugs. The previous reports demonstrated that p53 and RAS genes colud regulate the expression of MDR1 gene. However, there was no evidence of intranuclear expression of these gene products in human myelogenous leukemia cell line, KY-821 as well as its drug resistant sublines. Alternative expression of NF-kappaB or AP-1 transcription factors is speculated in these cell lines, because alternative regulation of cells growth of these cell lines with tumor necrosis factor alpha (TNF alpha) has been present. The expression of intranuclear NF-kappaB was enhanced with TNF alpha in KY-821, while it was not changed in drug resistant sublines. However, TNF alpha sensitive subclones of drug resistant cell lines expressend high level NF-kappaB after stimulation with TNF alpha. One of the other transcription factors, AP-1, was enhanced in both KY-821 and its drug resistant sublines after TNF alpha stimulation, indicating no association with resistance to TNF alpha and anticancer drugs. Furthermore, YB-1 is not expressed in cell lines used in this study, although YB-1 has been recently reported as a regulator of MDR1 gene. On the other hand, heat shock protein 27 (HSP27) and HSP70 have been expressed in the nucleus of cisplatin resistant human ovarian carcinoma cell line, TYK-R10, with showed multidrug resistant characteristics without MDR1 gene expression. Heat shock treatment enhanced the expression of HSPs as well as drug resistant level. Thus further examinations should be needed to elucidate what transcripton factors including HSPs are closely associated with drug resistance.
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Research Products
(3 results)
