BACKGROUND: Castration-resistant prostate cancer (CRPC) represents a therapeutic challenge for current medications. METHODS: In order to explore the molecular mechanisms involved in CRPC progression and to identify new therapeutic targets, we analyzed a unique sample set of 11 CRPCs and 7 advanced tumors by array-CGH and gene expression microarrays. The genome-wide DNA and RNA data were integrated to identify genes whose overexpression was driven by their amplification. To assess the functional role of these genes, their expression was analyzed in a transcriptional data set of 329 clinical prostate cancers and the corresponding gene products were silenced using RNA interference in prostate cancer cells. RESULTS: Six recurrent genetic targets were identified in the CRPCs; ATP1B1, AR, FAM110B, LAS1L, MYC, and YIPF6. In addition to AR and MYC, FAM110B emerged as a potential key gene involved in CRPC progression in a subset of the tumors. FAM110B was able to regulate AR signaling in prostate cancer cells and FAM110B itself was regulated by androgens. FAM110B siRNA inhibited the growth of prostate cancer cells in vitro, and this effect was substantially enhanced in androgen deficient conditions. Ectopic FAM110B expression in non-cancerous epithelial prostate cells induced aneuploidy and impaired antigen presentation. CONCLUSIONS: The DNA/RNA gene outlier detection combined with siRNA cell proliferation assay identified FAM110B as a potential growth promoting key gene for CRPC. FAM110B appears to have a key role in the androgen signaling and progression of CRPC impacting multiple cancer hallmarks and therefore highlighting a potential therapeutic target.
BACKGROUND: Castration-resistant prostate cancer (CRPC) represents a therapeutic challenge for current medications. METHODS: In order to explore the molecular mechanisms involved in CRPC progression and to identify new therapeutic targets, we analyzed a unique sample set of 11 CRPCs and 7 advanced tumors by array-CGH and gene expression microarrays. The genome-wide DNA and RNA data were integrated to identify genes whose overexpression was driven by their amplification. To assess the functional role of these genes, their expression was analyzed in a transcriptional data set of 329 clinical prostate cancers and the corresponding gene products were silenced using RNA interference in prostate cancer cells. RESULTS: Six recurrent genetic targets were identified in the CRPCs; ATP1B1, AR, FAM110B, LAS1L, MYC, and YIPF6. In addition to AR and MYC, FAM110B emerged as a potential key gene involved in CRPC progression in a subset of the tumors. FAM110B was able to regulate AR signaling in prostate cancer cells and FAM110B itself was regulated by androgens. FAM110B siRNA inhibited the growth of prostate cancer cells in vitro, and this effect was substantially enhanced in androgen deficient conditions. Ectopic FAM110B expression in non-cancerous epithelial prostate cells induced aneuploidy and impaired antigen presentation. CONCLUSIONS: The DNA/RNA gene outlier detection combined with siRNA cell proliferation assay identified FAM110B as a potential growth promoting key gene for CRPC. FAM110B appears to have a key role in the androgen signaling and progression of CRPC impacting multiple cancer hallmarks and therefore highlighting a potential therapeutic target.
Authors: Shanshan Zhao; Milan S Geybels; Amy Leonardson; Rohina Rubicz; Suzanne Kolb; Qingxiang Yan; Brandy Klotzle; Marina Bibikova; Antonio Hurtado-Coll; Dean Troyer; Raymond Lance; Daniel W Lin; Jonathan L Wright; Elaine A Ostrander; Jian-Bing Fan; Ziding Feng; Janet L Stanford Journal: Clin Cancer Res Date: 2016-06-29 Impact factor: 12.531
Authors: René Böttcher; Charlotte F Kweldam; Julie Livingstone; Emilie Lalonde; Takafumi N Yamaguchi; Vincent Huang; Fouad Yousif; Michael Fraser; Robert G Bristow; Theodorus van der Kwast; Paul C Boutros; Guido Jenster; Geert J L H van Leenders Journal: BMC Cancer Date: 2018-01-02 Impact factor: 4.430
Authors: Anastasia Meshcheryakova; Martin Svoboda; Ammar Tahir; Harald C Köfeler; Alexander Triebl; Felicitas Mungenast; Georg Heinze; Christopher Gerner; Philip Zimmermann; Markus Jaritz; Diana Mechtcheriakova Journal: Oncotarget Date: 2016-04-19
Authors: Jin Zhou; Timothy G Jenkins; Alesia M Jung; Kyoung Sook Jeong; Jing Zhai; Elizabeth T Jacobs; Stephanie C Griffin; Devi Dearmon-Moore; Sally R Littau; Wayne F Peate; Nathan A Ellis; Peter Lance; Yin Chen; Jefferey L Burgess Journal: PLoS One Date: 2019-03-26 Impact factor: 3.240