2011
DOI: 10.1158/2159-8290.cd-11-0130
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Molecular Characterization of Neuroendocrine Prostate Cancer and Identification of New Drug Targets

Abstract: Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer that most commonly evolves from preexisting prostate adenocarcinoma (PCA). Using Next Generation RNA-sequencing and oligonucleotide arrays, we profiled 7 NEPC, 30 PCA, and 5 benign prostate tissue (BEN), and validated findings on tumors from a large cohort of patients (37 NEPC, 169 PCA, 22 BEN) using IHC and FISH. We discovered significant overexpression and gene amplification of AURKA and MYCN in 40% of NEPC and 5% of PCA, respe… Show more

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Cited by 817 publications
(1,079 citation statements)
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References 27 publications
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“…We are the first to show a strong correlation between high active b-catenin immunohistochemical expression and high Gleason score prostate tumors. Many studies have linked overexpression of AurKA with progression and malignant phenotype of prostate cancers (41)(42)(43)(44), although there are controversial results with respect to its correlation with the Gleason score (45,46). We observed a significant correlation between high expression of AurKA and high Gleason score tumors.…”
Section: Discussionmentioning
confidence: 50%
“…We are the first to show a strong correlation between high active b-catenin immunohistochemical expression and high Gleason score prostate tumors. Many studies have linked overexpression of AurKA with progression and malignant phenotype of prostate cancers (41)(42)(43)(44), although there are controversial results with respect to its correlation with the Gleason score (45,46). We observed a significant correlation between high expression of AurKA and high Gleason score tumors.…”
Section: Discussionmentioning
confidence: 50%
“…Similarly, short hairpin RNA (shRNA)-mediated silencing of N-myc in neuroblastoma cells has identified a 157 target-gene panel including those involved cell cycle, DNA repair, and neuronal differentiation genes; this panel has been associated with poor prognosis in patients with neuroblastoma. More recently, a similar set of N-myc-targeted genes has been observed in neuroendocrine prostate cancer, with upregulation of cell cycle and neuroendocrine type genes (35,56). In prostate cancer, Nmyc binds neuroendocrine and androgen-regulated gene promoters, suggesting direct involvement in neuroendocrine transformation.…”
Section: Functional Targets Of N-mycmentioning
confidence: 61%
“…N-myc amplification rarely occurs in other lung cancer histologies. N-myc amplification also occurs in approximately 40% of neuroendocrine/small-cell prostate cancers, is commonly seen concurrently with amplification of the aurora kinase A gene (AURKA), and associated with poor prognosis (35,36). In both small-cell lung and prostate cancers, N-myc amplification may occur early before the development of metastasis.…”
Section: N-myc and Human Cancermentioning
confidence: 99%
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“…VAV2 is a coactivator of androgen receptor (AR) and sustains AR signaling under androgen deprivation therapy (ADT) (Magani et al ., 2017); it also promotes angiogenesis and metastasis (Barrio‐Real and Kazanietz, 2012). AURKA plays a critical role in mitosis (Dominguez‐Brauer et al ., 2015; Plotnikova et al ., 2015) and promotes the development of neuroendocrine PC under ADT (Beltran et al ., 2011; Mosquera et al ., 2013). DNMT3B may regulate epigenetic events to facilitate CRPC development (Hoffmann et al ., 2007).…”
Section: Resultsmentioning
confidence: 99%