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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3892

Title: Disabled Homolog 2 (DAB2) Protein in Tumor Microenvironment Correlates with Aggressive Phenotype in Human Urothelial Carcinoma of the Bladder.
Other Titles: 尿路上皮癌微小環境内におけるDisabled Homolog 2 (DAB2) は腫瘍細胞上皮間葉転換を介して遊走能・浸潤能を高める
Authors: Itami, Yoshitaka
Miyake, Makito
Ohnishi, Sayuri
Tatsumi, Yoshihiro
Gotoh, Daisuke
Hori, Shunta
Morizawa, Yosuke
Iida, Kota
Ohnishi, Kenta
Nakai, Yasushi
Inoue, Takeshi
Anai, Satoshi
Tanaka, Nobumichi
Fujii, Tomomi
Shimada, Keiji
Furuya, Hideki
Khadka, Vedbar S
Deng, Youping
Fujimoto, Kiyohide
Keywords: DAB2
bladder cancer
epithelial-mesenchymal transition
Issue Date: 20-Jan-2020
Publisher: MDPI
Citation: Diagnostics Vol.10 No.1 Article No.54 (2020 Jan)
Abstract: Disabled homolog-2 (DAB2) has been reported to be a tumor suppressor gene. However, a number of contrary studies suggested that DAB2 promotes tumor invasion in urothelial carcinoma of the bladder (UCB). Here, we investigated the clinical role and biological function of DAB2 in human UCB. Immunohistochemical staining analysis for DAB2 was carried out on UCB tissue specimens. DAB2 expression levels were compared with clinicopathological factors. DAB2 was knocked-down by small interfering RNA (siRNA) transfection, and then its effects on cell proliferation, invasion, and migration, and changes to epithelial-mesenchymal transition (EMT)-related proteins were evaluated. In our in vivo assays, tumor-bearing athymic nude mice subcutaneously inoculated with human UCB cells (MGH-U-3 or UM-UC-3) were treated by DAB2-targeting siRNA. Higher expression of DAB2 was associated with higher clinical T category, high tumor grade, and poor oncological outcome. The knock-down of DAB2 decreased both invasion and migration ability and expression of EMT-related proteins. Significant inhibitory effects on tumor growth and invasion were observed in xenograft tumors of UM-UC-3 treated by DAB2-targeting siRNA. Our findings suggested that DAB2 expression was associated with poor prognosis through increased oncogenic properties including tumor proliferation, migration, invasion, and enhancement of EMT in human UCB.
Description: 博士(医学)・甲第768号・令和3年3月15日
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
URI: http://hdl.handle.net/10564/3892
ISSN: 20754418
Academic Degrees and number: 24601A768
Degree-granting date: 2021-03-15
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2020年度

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