An in vitro system to characterize prostate cancer progression identified signaling required for self-renewal

フォーマット:

論文

責任表示:

Salah, Mohammed ; Nishimoto, Yuuki ; Kohno, Susumu ; Kondoh, Atsushi ; Kitajima, Shunsuke ; Muranaka, Hayato ; Nishiuchi, Takumi ; Ibrahim, Ahmed ; Yoshida, Akiyo ; Takahashi, Chiaki

言語:

英語

出版情報:

John Wiley and Sons, 2016-12-01

著者名:

Salah, Mohammed

Nishimoto, Yuuki

Kohno, Susumu

Kondoh, Atsushi

Kitajima, Shunsuke

Muranaka, Hayato

Nishiuchi, Takumi

Ibrahim, Ahmed

Yoshida, Akiyo

Takahashi, Chiaki

続きを見る

掲載情報:

Molecular Carcinogenesis

ISSN:

0899-1987      

巻:

55

通号:

12

開始ページ:

1974

終了ページ:

1989

バージョン:

author

概要:

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.<br />Embargo Period 12 months 続きを見る

URL:

http://hdl.handle.net/2297/46761