Specific and redundant activities of ETV1 and ETV4 in prostate cancer aggressiveness revealed by co-overexpression cellular contexts

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Mesquita, D (Author) Other; Barros Silva, JD (Author) Other; Santos, J (Author) Other; Skotheim, RI (Author) Other; Lothe, RA (Author) Other; Paulo, P (Author) Other; Manuel R Teixeira (Author) ICBAS

Journal

Title: Oncotarget

Vol. 6

Pages: 5217-5236

ISSN: 1949-2553

Publisher: Impact Journals

Indexing

ISI Web of Knowledge - 15 Citations

Scopus - 16 Citations

Other information

Authenticus ID: P-00A-9H5

DOI: 10.18632/oncotarget.2847

Abstract (EN): Genomic rearrangements involving ETS transcription factors are found in 50-70% of prostate carcinomas. While the large majority of the rearrangements involve ERG, around 10% involve members of the PEA3 subfamily (ETV1, ETV4 and ETV5). Using a panel of prostate cancer cell lines we found co-overexpression of ETV1 and ETV4 in two cell line models of advanced prostate cancer (MDA-PCa-2b and PC3) and questioned whether these PEA3 family members would cooperate in the acquisition of oncogenic properties or show functional redundancy. Using shRNAs we found that ETV1 and ETV4 have partially overlapping functions, with ETV1 being more relevant for cell invasion and ETV4 for anchorage-independent growth. In vitro expression signatures revealed the regulation of both specific and shared candidate targets that may resemble cellular mechanisms in vivo by interaction with the same intermediate partners. By combining the phenotypic impact data and the gene expression profiles of in vitro models with clinico-pathological features and gene expression profiles of ETS-subtyped tumors, we identified a set of eight genes associated with advanced stage and a set of three genes associated with higher Gleason score, supporting an oncogenic role of ETV1 and ETV4 overexpression and revealing gene sets that may be useful as prognostic markers.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 20