title: Uncovering potential downstream targets of oncogenic GRPR overexpression in prostate carcinomas harboring ETS rearrangements.
abstract: 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, PKCε, 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.
authors.affiliation: Department of Genetics and Cancer Genetics Group - CI-IPOP, Portuguese Oncology Institute-Porto, Rua Dr. António Bernardino de Almeida, Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Santos
authors.affiliation: Department of Genetics and Cancer Genetics Group - CI-IPOP, Portuguese Oncology Institute-Porto, Rua Dr. António Bernardino de Almeida, Porto, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Mesquita
authors.affiliation: Department of Genetics and Cancer Genetics Group - CI-IPOP, Portuguese Oncology Institute-Porto, Rua Dr. António Bernardino de Almeida, Porto, Portugal.
authors.forename: João D
authors.initials: JD
authors.lastname: Barros-Silva
authors.affiliation: Cancer Biology and Epigenetics Group - CI-IPOP, Portuguese Oncology Institute-Porto, Rua Dr. António Bernardino de Almeida, Porto, Portugal ; Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira, Porto, Portugal.
authors.forename: Carmen
authors.initials: C
authors.lastname: Jerónimo
authors.affiliation: Cancer Biology and Epigenetics Group - CI-IPOP, Portuguese Oncology Institute-Porto, Rua Dr. António Bernardino de Almeida, Porto, Portugal ; Department of Pathology, Portuguese Oncology Institute-Porto, Rua Dr. António Bernardino de Almeida, Porto, Portugal ; Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Henrique
authors.affiliation: Department of Urology, Portuguese Oncology Institute-Porto, Rua Dr. António Bernardino de Almeida, Porto, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Morais
authors.affiliation: Department of Genetics and Cancer Genetics Group - CI-IPOP, Portuguese Oncology Institute-Porto, Rua Dr. António Bernardino de Almeida, Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Paulo
authors.affiliation: Department of Genetics and Cancer Genetics Group - CI-IPOP, Portuguese Oncology Institute-Porto, Rua Dr. António Bernardino de Almeida, Porto, Portugal ; Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira, Porto, Portugal.
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Teixeira
keywords: ETS positive tumors; GRPR overexpression; oncogenic role; prostate cancer; target genes