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Integrative genomic, transcriptomic, and RNAi analysis indicates a potential oncogenic role for FAM110B in castration‐resistant prostate cancer
Author(s) -
Vainio Paula,
Wolf Maija,
Edgren Henrik,
He Tao,
Kohonen Pekka,
Mpindi JohnPatrick,
Smit Frank,
Verhaegh Gerald,
Schalken Jack,
Perälä Merja,
Iljin Kristiina,
Kallioniemi Olli
Publication year - 2011
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21487
Subject(s) - prostate cancer , cancer research , biology , chromoplexy , rna interference , transcriptome , cancer , prostate , gene , ectopic expression , pca3 , rna , gene expression , genetics
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. Prostate 72:789–802, 2012. © 2011 Wiley Periodicals, Inc.