| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2017-12-05 |
| タイトル |
|
|
タイトル |
An in vitro system to characterize prostate cancer progression identified signaling required for self-renewal |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| ID登録 |
|
|
ID登録 |
10.24517/00027473 |
|
ID登録タイプ |
JaLC |
| 著者 |
Salah, Mohammed
Nishimoto, Yuuki
Kohno, Susumu
Kondoh, Atsushi
Kitajima, Shunsuke
Muranaka, Hayato
Nishiuchi, Takumi
Ibrahim, Ahmed
Yoshida, Akiyo
Takahashi, Chiaki
|
| 著者別表示 |
河野, 晋
北嶋, 俊輔
西内, 巧
高橋, 智聡
|
| 提供者所属 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
金沢大学がん進展制御研究所 |
| 書誌情報 |
Molecular Carcinogenesis
巻 55,
号 12,
p. 1974-1989,
発行日 2016-12-01
|
| ISSN |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
0899-1987 |
| NCID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA10671664 |
| DOI |
|
|
関連タイプ |
isVersionOf |
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.1002/mc.22444 |
| 出版者 |
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|
出版者 |
John Wiley and Sons |
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Mutations in RB and PTEN are linked to castration resistance and poor prognosis in prostate cancer. Identification of genes that are regulated by these tumor suppressors in a context that recapitulates cancer progression may be beneficial for discovering novel therapeutic targets. Although various genetically engineered mice thus far provided tumor models with various pathological stages, they are not ideal for detecting dynamic changes in gene transcription. Additionally, it is difficult to achieve an effect specific to tumor progression via gain of functions of these genes. In this study, we developed an in vitro model to help identify RB- and PTEN-loss signatures during the malignant progression of prostate cancers. Trp53−/−; Rbf/f, Trp53−/−; Ptenf/f, and Trp53−/−; Rbf/f; Ptenf/f prostate epithelial cells were infected with AD-LacZ or AD-Cre. We found that deletion of Rb, Pten or both stimulated prostasphere formation and tumor development in immune-compromised mice. The GO analysis of genes affected by the deletion of Rb or Pten in Trp53−/− prostate epithelial cells identified a number of genes encoding cytokines, chemokines and extracellular matrix remodeling factors, but only few genes related to cell cycle progression. Two genes (Il-6 and Lox) were further analyzed. Blockade of Il-6 signaling and depletion of Lox significantly attenuated prostasphere formation in 3D culture, and in the case of IL-6, strongly suppressed tumor growth in vivo. These findings suggest that our in vitro model may be instrumental in identifying novel therapeutic targets of prostate cancer progression, and further underscore IL-6 and LOX as promising therapeutic targets. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc. |
| 内容記述 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
Embargo Period 12 months |
| 著者版フラグ |
|
|
出版タイプ |
AM |
|
出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
CA-PR-TAKAHASHI-C-1974.pdf (2.4 MB)
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