2007 Fiscal Year Final Research Report Summary
Potential Role of Xenobiotics Receptor PXR in Endometrial Cancer
| Project/Area Number |
17591739
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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 |
Obstetrics and gynecology
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| Research Institution | Okayama University |
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Principal Investigator |
MASUYAMA Hisashi Okayama University, University Hospital, Senior Assistant Professor (30314678)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAMATSU Yuji Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor (80218817)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Endometrial cancer / Drug resistance / Nuclear receotor |
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| Research Abstract |
Recent studies have revealed that pregnane X receptor (PXR) can function as a master regulator to control the expression of drug-metabolizing enzymes, cytochrome P-450 3A (CYP3A) family, as well as members of the drug transporter family, including multiple drug resistance 1 (MDR1). Previously, we demonstrated that steroid/xenobiotic metabolism by tumor tissue through the PXR-CYP3A pathway might play an important role in endometrial cancer, and that PXR ligands enhance PXR-mediated transcription in a ligand- and promoter-dependent fashion, leading to differential regulation of individual PXR targets, especially CYP3A4 and MDR1.
In this study, we investigated the potential contribution of PXR down-regulation by RNA interference toward the augmentation of drug sensitivity and the overcoming of drug resistance. We observed the protein levels of both CYP3A4 and MDR1 in PXR siRNA-transfected cells were not increased in the presence of PXR ligands, paclitaxel, cisplatin, estradiol or medroxyprogesterone acetate (MPA), compared with control siRNA-transfected cells. There was no PXR-mediated transactivation or augmentation of transcription by coactivators in the presence of these ligands. We then found that PXR down-regulation caused a significant increase in cell growth inhibition and enhancement of apoptosis in the presence of the anti-cancer agents, paclitaxel, cisplatin and MPA. Finally, we demonstrated that PXR overexpression caused a significant decrease in cell growth inhibition and inhibited apoptosis in the presence of paclitaxel or cisplatin.
These data suggest that PXR down-regulation could be a novel therapeutic approach for the augmentation of sensitivity to anticancer agents, or to overcome resistance to them, in the treatment of endometrial cancer.
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[Journal Article] Elevated Serum sFlt-1/Ang-2 Ratio in Women with Preeclampsia2007
Author(s)
K., Hirokoshi, Y., Maeshima, K., Kobayashi, E., Matsuura, H., Sugiyama, Y., Yamasaki, H., Masuyama, Y., Hiramatsu, H., Makino
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Journal Title
Nephron Clin Pract 106
Pages: 43-50
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Circulating angiogenic factors in preeclampsia, gestational proteinuria, and preeclampsia superimposed on chronic glomerulonephritis2006
Author(s)
H., Masuyama, N., Suwaki, H., Nakatsukasa, A., Masumoto, Y., Tateishi, Y., Hiramatrsu
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Journal Title
Am J Obstet Gynecol 194
Pages: 551-556
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hypo-adiponectinemia and circulating angiogenic factors in overweight patients complicated with preeclampsia2006
Author(s)
N., Suwaki, H., Masuyama, H., Nakatsukasa, A., Masumoto, Y., Sumida, N., Takamoto, Y., Hiramatrsu
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Journal Title
Am J Obstet Gynecol 195
Pages: 1687-1692
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hiramatrsu The Role of Constitutive,Androstane Receptor in the Pathoohysiology of Neonatal Jaundice2006
Author(s)
N., Nakatsukasa, H., Masuyama, A., Masumoto, N., Suwaki, T., Segawa, Y., Sumida, Y., Tateishi, H., Inoshita, N., Takamoto, Y
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Journal Title
Journal of the Japan Society for Study of Women's Nutrition and metabolism 12
Pages: 39-40
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The Pregnane X Receptor Regulates Gene Expression in a Ligand- and Promoter-selective Fashion2005
Author(s)
H., Masuyama, N., Suwaki, Y., Tateishi, H., Nakatsukasa, T., Segawa, Y., Hiramatsu
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Journal Title
Mot Endocrinol 19
Pages: 1170-1180
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Increase of serum angiopoietin-2 during pregnancy is suppressed in women with preeclampsia2005
Author(s)
K., Hirokoshi, Y., Maeshima, K., Kobayashi, E., Matsuura, H., Sugiyama, Y., Yamasaki, H., Masuyama, Y., Hiramatsu, H., Makino
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Journal Title
Am J Hypertens 18(9)
Pages: 1181-1188
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel Regulation Mechanism of Steroids / Xenobiotics through nuclear recentor. PXR2005
Author(s)
H., Masuyama, N., Nakatsukasa, A., Masumoto, N., Suwaki, T., Segawa, Y., Tateishi, H., Inoshita, Y., Mlzutani, Y., Hiramatrsu
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Journal Title
Journal of the japan Society for Study of Women's Nutrition and metabolism 11
Pages: 66-67
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Essential Role of Nuclear Orphan Receptor COUP-TFII for gastric Pattering during Development and Association with Generation of Congenital Diaphragmatic Hernia2007
Author(s)
N., Takamoto, S., Inoue, Y., Akahori, H., Nakatsukasa, A., Masumoto, Y., Sumida, H., Masuyama, Y., Hiramatsu, S., Tsai, MJ., Tsai
Organizer
The 58th Annual Congress of Japanese Society of Developmental Biologists
Place of Presentation
Fukuoka, Japan
Year and Date
20070428-30
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The Potential Role of Angiogenic Factors and Adiponectin in the Pathophysiology of Preeclampsia2007
Author(s)
N., Suwaki, H., Masuyama, Y., Akahori, H., Nakatsukasa, S., Inoue, A., Masumoto, Y., Sumida, T., Segawa, N., Takamoto, Y., Hiramatsu
Organizer
The 59th Annual Congress of the Japan Society of Obstetrics and Gynecology
Place of Presentation
Kyoto, Japan
Year and Date
20070414-17
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 核内受容体CARの新生児黄疸発症機序への関与2006
Author(s)
中務日出輝, 増山 寿, 井上誠司, 舛本明生, 洲脇尚子, 住田由美, 瀬川友功, 高本憲男, 平松祐司
Organizer
第30回日本産科婦人科栄養代謝研究会
Place of Presentation
東京
Year and Date
20060825-26
Description
「研究成果報告書概要(和文)」より
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[Presentation] The Role of New Nuclear Receptor, CAR in Neonatal Jaundice2006
Author(s)
H., Nakatsukasa, H., Masuyama, S., Inoue, A., Masumoto, N., Suwaki, Y., Sumida, N., Takamoto, Y., Hiramatsu
Organizer
The 30th Annual Congress of the Japan Society for Women's Nutrition and Metabolism
Place of Presentation
Tokyo, Japan
Year and Date
20060825-26
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Essential Role of Nuclear Orphan Receptor COUP-TM for gastric Pattering during Development and Association with Generation of Congenital Diaphragmatic Hernia.2006
Author(s)
N., Takamoto, S., Inoue, Y., Akahori, A., Masumoto, Y., Sumida, H., Masuyama, Y., Hiramatsu
Organizer
The 31st Annual Congress of the Japan Society for Women's Nutrition and Metabolism
Place of Presentation
Okayama, Japan
Year and Date
20060810-11
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 核内受容体CARの新生児黄疸発症機序への関与2006
Author(s)
中務日出輝, 増山 寿, 井上誠司, 舛本明生, 洲脇尚子, 住田由美, 高本憲男, 平松祐司
Organizer
第42回日本周産期・新生児学会総会および学術集会
Place of Presentation
宮崎
Year and Date
20060709-11
Description
「研究成果報告書概要(和文)」より
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[Presentation] The Potential Role of Obesity and Angiogenic Factors in the Pathophysiology of Preeclampsia2006
Author(s)
H., Masuyama, N., Suwaki, H., Nakatsukasa, S., Inoue, A., Masumoto, Y., Sumida, N., Takamoto, Y., Hiramatsu
Organizer
The 42nd Annual Congress of Japan Society of Perinatal and Neonatal Medicine
Place of Presentation
Miyazaki, Japan
Year and Date
20060709-11
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The Role of New Nuclear Receptor, CAR in Neonatal Jaundice2006
Author(s)
H., Nakatsukasa, H., Masuyama, S., Inoue, A., Masumoto, N., Suwaki, Y., Sumida, N., Takamoto, Y., Hiramatsu
Organizer
The 42nd Annual Congress of Japan Society of Perinatal and Neonatal Medicine
Place of Presentation
Miyazaki, Japan
Year and Date
20060709-11
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The PXR Suppression on the Effect of Anti-tumor Drugs in Endometrial Cancer2006
Author(s)
H., Masuyama, H., Nakatsukasa, N., Suwaki, T., Segawa, N., Takamoto, Y., Hiramatsu
Organizer
The 80th Annual Congress of the Japan Endocrine Society
Place of Presentation
Tokyo, Japan
Year and Date
20060614-16
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 妊婦のインスリン抵抗性の評価2006
Author(s)
洲脇尚子, 舛本明生, 住田由美, 井上誠司, 高本憲男, 増山 寿, 平松祐司
Organizer
第79回日本内分泌学会
Place of Presentation
神戸
Year and Date
20060519-21
Description
「研究成果報告書概要(和文)」より
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[Presentation] Insulin Resistance in Pregnancy2006
Author(s)
N., Suwaki, A., Masumoto, Y., Sumida, S., Inoshita, N., Takamoto, H., Masuyama, Y., Hiramatsu
Organizer
The 79th Annual Congress of the Japan Endocrine Society
Place of Presentation
Kobe, Japan
Year and Date
20060519-21
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The Potential Role of Obesity in the Pathophysiology of Preeclampsia2006
Author(s)
H., Masuyama, N., Suwaki, H., Nakatsukasa, S., Inoue, A., Masumoto, Y., Sumida, N., Takamoto, Y., Hiramatsu
Organizer
The 79th Annual Congress of the Japan Endocrine Society
Place of Presentation
Kobe, Japan
Year and Date
20060519-21
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 核内受容体CARの新生児発症機序への関与2006
Author(s)
中務日出輝, 増山 寿, 井上誠司, 舛本明生, 洲脇尚子, 瀬川友功, 住田由美, 立石洋子, 井下秀司, 高本憲男, 平松祐司
Organizer
第58回日本産科婦人科学会
Place of Presentation
横浜
Year and Date
20060421-25
Description
「研究成果報告書概要(和文)」より
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[Presentation] The Function of Nuclear Orphan Receptor COUP-TFII in Female Reproduction2006
Author(s)
N., Takamoto, S., Inoue, A., Masumoto, H., Nakatsukasa, N., Suwaki, H., Masuyama, Y., Hiramatsu
Organizer
The 58th Annual Congress of the Japan Society of Obstetrics and Gynecology
Place of Presentation
Yokohama, Japan
Year and Date
20060421-25
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The Potential Role cif Obesity and Adiponectin in the Pathophysiology of Preeclampsia2006
Author(s)
N., Suwaki, H., Masuyama, A.,Masumoto, H., Nakatsukasa, Y., Sumida, Y., Tateishi, H., Inoshita, N., Takamoto, Y., Hiramatsu
Organizer
The 58th Annual Congress of the Japan Society of Obstetrics and Gynecology
Place of Presentation
Yokohama, Japan
Year and Date
20060421-25
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Relationship between Advanced Glycation End Products (AGES) and Fetal Growth in Pregnant Mice Model with Diabetes2006
Author(s)
A., Masumoto, H., Nakatsukasa, N., Suwaki, T., Segawa, Y., Sumida, Y., Tateishi, H., Inoshita, N., Takamoto, H., Masuyama, Y., Hiramatsu
Organizer
The 58th Annual Congress of the Japan Society of Obstetrics and Gynecology
Place of Presentation
Yokohama, Japan
Year and Date
20060421-25
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The Ontogeny of Angiogenic Factors in Preeclampsia, Gestational Proteinuria and Normal Pregnancy2006
Author(s)
H., Masuyama, H., Nakatsukasa, A., Masumoto, N., Suwaki, Y., Sumida, Y., Tateishi, H., Inoshita, N., Takamoto, Y., Hiramatsu
Organizer
The 58th Annual Congress of the Japan Society of Obstetrics and Gynecology
Place of Presentation
Yokohama, Japan
Year and Date
20060421-25
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The Role of New Nuclear Receptor, CAR in Neonatal Jaundice2006
Author(s)
H., Nakatsukasa, H., Masuyama, S., Inoue, A., Masumoto, N., Suwaki, T., Segawa, Y., Sumida, Y., Tateishi, H., Inoshita, N., Takamoto, Y., Hiramatsu
Organizer
The 58th Annual Congress of the Japan Society of Obstetrics and Gynecology
Place of Presentation
Yokohama, Japan
Year and Date
20060421-25
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The Relationship of Peroxisome Proliferator activated Receptor gamma and Angiogenic Factor in Placentation of Diabetic Pregnancy2005
Author(s)
N., Suwaki, H., Masuyama, A., Masumoto, N., Takamoto, Y.,Hiramatsu
Organizer
The 13rd Annual Congress of Japan Placenta Association
Place of Presentation
Toyama, Japan
Year and Date
20051027-28
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 新しい核内受容体CARの新生児黄疸への関与2005
Author(s)
中務日出輝, 増山 寿, 舛本明生, 洲脇尚子, 瀬川友巧, 住田由美, 立石洋子, 井下秀司, 高本憲男, 平松祐司
Organizer
第29回日本産科婦人科栄養・代謝研究会
Place of Presentation
秋田
Year and Date
20050729-30
Description
「研究成果報告書概要(和文)」より
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[Presentation] The Role of New Nuclear Receptor, CAR in Neonatal Jaundice2005
Author(s)
H., Nakatsukasa, H., Masuyama, A., Masumoto, N., Suwaki, T., Segawa, Y., Sumida, Y., Tateishi, H., Inoshita, N., Takamoto, Y., Hiramatsu
Organizer
The 29th Annual Congress of the Japan Society for Women's Nutrition and Metabolism
Place of Presentation
Akita, Japan
Year and Date
20050729-30
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The Investigation for Drug Metabolism and Resistance through PXR in Endometrial Cancer2005
Author(s)
H., Masuyama, H., Nakatsukasa, N., Suwaki, Y., Tateishi, T., Segawa, Y., Hiramatsu
Organizer
The 78th Annual Congress of the Japan Endocrine Society
Place of Presentation
Tokyo, Japan
Year and Date
20050701-03
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 糖尿病合併妊娠の胎盤形成における Peroxisome Proliferator Activated Receptor γ と血管増殖因子に関する検討2005
Author(s)
洲脇尚子, 増山 寿, 井上誠司, 中務日出輝, 舛本明生, 瀬川友功, 住田由美, 立石洋子, 井下秀司, 高本憲男, 平松祐司
Organizer
第58回日本産科婦人科学会中国・四国合同地方部会
Place of Presentation
宇部
Year and Date
2005-10-15
Description
「研究成果報告書概要(和文)」より
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[Presentation] The Relationship of Peroxisome Proliferator -activated Receptor gamma and Angiogenic Factor in Placentation of Diabetic Pregnancy2005
Author(s)
N., Suwaki, H., Masuyama, A., Masumoto, Y., Tateishi, H., Inoshita, N., Takamoto, Y., Hiramatsu
Organizer
The 58th Annual Congress of Chugoku and Shikoku Districts of the Japan Society of Obstetrics and Gynecology
Place of Presentation
Ube, Japan
Year and Date
2005-10-15
Description
「研究成果報告書概要(欧文)」より
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