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Uncovering potential downstream targets of oncogenic GRPR overexpression in prostate carcinomas harboring ETS rearrangements

Title
Uncovering potential downstream targets of oncogenic GRPR overexpression in prostate carcinomas harboring ETS rearrangements
Type
Article in International Scientific Journal
Year
2015
Authors
Santos, J
(Author)
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Mesquita, D
(Author)
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Barros Silva, JD
(Author)
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Jerónimo, C
(Author)
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Henrique, R
(Author)
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Morais, A
(Author)
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Paulo, P
(Author)
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Journal
Title: OncoscienceImported from Authenticus Search for Journal Publications
Vol. 2 No. 5
Pages: 497-507
ISSN: 2331-4737
Publisher: Impact Journals
Indexing
Other information
Authenticus ID: P-00K-71V
Abstract (EN): Gastrin-releasing peptide receptor (GRPR) is known to be overexpressed in several human malignancies, including prostate cancer, and has been implicated in multiple important neoplastic signaling pathways. We recently have shown that GRPR is an ERG and ETV1 target gene in prostate cancer, using a genome-wide scale and exon-level expression microarray platform. Due to its cellular localization, the relevance of its function and the availability of blocking agents, GRPR seems to be a promising candidate as therapeutic target. Our present work shows that effective knockdown of GRPR in LNCaP and VCaP cells attenuates their malignant phenotype by decreasing proliferation, invasion and anchorage-independent growth, while increasing apoptosis. Using an antibody microarray we were able to validate known and identify new targets of GRPR pathway, namely AKT1, PKCe, TYK2 and MST1. Finally, we show that overexpression of these GRPR targets is restricted to prostate carcinomas harboring ERG and/or ETV1 rearrangements, establishing their potential as therapeutic targets for these particular molecular subsets of the disease.
Language: English
Type (Professor's evaluation): Scientific
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