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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/2749

Title: Inhibition of cell death and induction of G2 arrest accumulation in human ovarian clear cells by HNF-1β transcription factor: chemosensitivity is regulated by checkpoint kinase CHK1.
Other Titles: 卵巣明細胞腺癌における転写因子HNF-1βはDNA損傷チェックポイント機構の一つであるCHK1タンパクを制御し、抗癌剤耐性を獲得する
Authors: Shigetomi, Hiroshi
Sudo, Tamotsu
Shimada, Keiji
Uekuri, Chiharu
Tsuji, Yoriko
Kanayama, Seiji
Naruse, Katsuhiko
Yamada, Yoshihiko
Konishi, Noboru
Kobayashi, Hiroshi
Keywords: Transcription factors
DNA damage response
Cell cycle
Checkpoint control
Chemoresistance
Issue Date: Jun-2014
Publisher: Lippincott Williams & Wilkins
Citation: International journal of gynecological cancer Vol.24 No.5 p.838-843
Abstract: Objective Appropriate cell cycle checkpoints are essential for the maintenance of normal cells and chemosensitivity of cancer cells. Clear cell adenocarcinoma (CCA) of the ovary is highly resistant to chemotherapy. Hepatocyte nuclear factor-1β (HNF-1β) is known to be overexpressed in CCA, but its role and clinical significance is unclear. We investigated the role of HNF-1β in regulation of the cell cycle in CCA. Methods To clarify the effects of HNF-1β on cell cycle checkpoints, we compared the cell cycle distribution and the expression of key proteins involved in CCA cells in which HNF-1β had been stably knocked down and in vector-control cell lines after treatment with bleomycin. HNF-1β (+) cells were arrested in G2 phase because of DNA damage. Results HNF-1β (−) cells died because of a checkpoint mechanism. G2 arrest of HNF-1β (+) cells resulted from sustained CHK1 activation, a protein that plays a major role in the checkpoint mechanism. HNF-1β (+) cells were treated with a CHK1 inhibitor after bleomycin treatment. Flow cytometric analysis of the cell cycle demonstrated that DNA damage–induced G2-arrested cells were released from the checkpoint and killed by a CHK1 inhibitor. Conclusions The chemoresistance of CCA may be due to aberrant retention of the G2 checkpoint through overexpression of HNF-1β. This is the first study demonstrating cell cycle regulation and chemosensitization by a CHK1 inhibitor in CCA.
Description: 博士(医学)・乙第1345号・平成26年12月3日
© 2014 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.
URI: http://hdl.handle.net/10564/2749
ISSN: 1048891X
Academic Degrees and number: 24601B1345
Degree-granting date: 2014-12-03
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2014年度

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