SPOP Mutation Drives Prostate Tumorigenesis In Vivo through Coordinate Regulation of PI3K/mTOR and AR Signaling.

Blattner, Mirjam; Liu, Deli; Robinson, Brian D; Huang, Dennis; Poliakov, Anton; Gao, Dong; Nataraj, Srilakshmi; Deonarine, Lesa D; Augello, Michael A; Sailer, Verena; Ponnala, Lalit; Ittmann, Michael; Chinnaiyan, Arul M; Sboner, Andrea; Chen, Yu; Rubin, Mark Andrew; Barbieri, Christopher E (2017). SPOP Mutation Drives Prostate Tumorigenesis In Vivo through Coordinate Regulation of PI3K/mTOR and AR Signaling. Cancer cell, 31(3), pp. 436-451. Cell Press 10.1016/j.ccell.2017.02.004

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Recurrent point mutations in SPOP define a distinct molecular subclass of prostate cancer. Here, we describe a mouse model showing that mutant SPOP drives prostate tumorigenesis in vivo. Conditional expression of mutant SPOP in the prostate dramatically altered phenotypes in the setting of Pten loss, with early neoplastic lesions (high-grade prostatic intraepithelial neoplasia) with striking nuclear atypia and invasive, poorly differentiated carcinoma. In mouse prostate organoids, mutant SPOP drove increased proliferation and a transcriptional signature consistent with human prostate cancer. Using these models and human prostate cancer samples, we show that SPOP mutation activates both PI3K/mTOR and androgen receptor signaling, effectively uncoupling the normal negative feedback between these two pathways.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie

UniBE Contributor:

Rubin, Mark Andrew

Subjects:

500 Science
500 Science > 570 Life sciences; biology

ISSN:

1535-6108

Publisher:

Cell Press

Language:

English

Submitter:

Marla Rittiner

Date Deposited:

20 Feb 2018 11:00

Last Modified:

20 Feb 2018 11:00

Publisher DOI:

10.1016/j.ccell.2017.02.004

PubMed ID:

28292441

Uncontrolled Keywords:

PI3K/mTOR SPOP androgen receptor cancer genomics organoids prostate cancer proteomics transgenic mouse model

BORIS DOI:

10.7892/boris.110867

URI:

https://boris.unibe.ch/id/eprint/110867

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