SPOP mutation drives prostate tumorigenesis in vivo through coordinate regulation of PI3K/mTOR and AR signaling Journal Article
| Authors: | Blattner, M.; Liu, D.; Robinson, B. D.; Huang, D.; Poliakov, A.; Gao, D.; Nataraj, S.; Deonarine, L. D.; Augello, M. A.; Sailer, V.; Ponnala, L.; Ittmann, M.; Chinnaiyan, A. M.; Sboner, A.; Chen, Y.; Rubin, M. A.; Barbieri, C. E. |
| Article Title: | SPOP mutation drives prostate tumorigenesis in vivo through coordinate regulation of PI3K/mTOR and AR signaling |
| Abstract: | 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. © 2017 Elsevier Inc. |
| Keywords: | proteomics; prostate cancer; androgen receptor; cancer genomics; pi3k/mtor; transgenic mouse model; organoids; spop |
| Journal Title: | Cancer Cell |
| Volume: | 31 |
| Issue: | 3 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2017-03-13 |
| Start Page: | 436 |
| End Page: | 451 |
| Language: | English |
| DOI: | 10.1016/j.ccell.2017.02.004 |
| PROVIDER: | scopus |
| PUBMED: | 28292441 |
| PMCID: | PMC5384998 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 April 2017 -- Source: Scopus |
