PO-43 - Differential coagulation factor expression in neuroendocrine prostate cancer (PC), metastatic castrate-resistant PC, and localized prostatic adenocarcinoma

2016 ◽  
Vol 140 ◽  
pp. S192 ◽  
Author(s):  
H. Choe ◽  
A. Sboner ◽  
H. Beltran ◽  
D. Nanus ◽  
S.T. Tagawa
Keyword(s):  
Prostate Cancer ◽  
Coagulation Factor ◽  
Prostatic Adenocarcinoma ◽  
Neuroendocrine Prostate Cancer ◽  
Factor Expression ◽  
Castrate Resistant

Differential expression of PSMA and 18F-fluciclovine transporter genes in metastatic castrate-resistant and treatment-emergent small cell/neuroendocrine prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 24-24
Author(s):  
Carissa Chu ◽  
Mohammed Alshalalfa ◽  
Martin Sjöström ◽  
Shuang Zhao ◽  
Annika Herlemann ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Expression Profiles ◽  
Small Cell ◽  
Imaging Modalities ◽  
Primary Tumors ◽  
Neuroendocrine Prostate Cancer ◽  
Psma Pet ◽  
Pet Ct ◽  
Castrate Resistant ◽  
Psma Expression

24 Background: 18F-fluciclovine (Axumin) PET/CT imaging is recommended by the NCCN in the setting of biochemical recurrence, while prostate-specific membrane antigen (PSMA) PET/CT is preferred by the EAU. The utility of these methods in the post-androgen deprivation therapy (ADT) setting however, is less defined. Our objective was to compare relative gene expression of the molecular targets of these imaging modalities— fluciclovine transporter genes (LAT1-4, ASCT1-2) and PSMA—in metastatic castrate resistant prostate cancer (mCRPC) and treatment-emergent small cell/neuroendocrine prostate cancer (t-SCNC). Methods: Genome-wide expression profiles of five mCRPC cohorts (Aggarwal, Grasso, Kumar, Beltran, Robinson, et al) were used to characterize relative expression of fluciclovine transporter (LAT1-4, ASC1-2) and PSMA (FOLH1) genes. 3 cohorts (Kumar, Beltran, Aggarwal) were enriched with t-SCNC tumors. The GSE35988 cohort included primary tumors and mCRPC. RNA expression profiling methods were consistent within cohorts. Results: 518 mCRPC specimens were included. In the GSE35988 cohort, PSMA expression was downregulated in mCRPC when compared to primary localized tumors (p=0.01). PSMA expression was further depressed in t-SCNC when compared with mCRPC (p<0.001). Of the fluciclovine transporter genes, LAT1 and LAT4 were overexpressed in mCRPC when compared to primary tumors, while ASC2 was less expressed (p<0.001). LAT1 was further overexpressed in t-SCNC when compared to mCRPC, while LAT2 was less expressed (p<0.001). PSMA expression was negatively correlated with LAT1 (p<0.001) but positively correlated with LAT2 (p=0.006). Other fluciclovine transporters were not correlated. Conclusions: Expression of PSMA and a subset of fluciclovine transporter genes are inversely correlated in mCRPC and t-SCNC. These findings suggest that fluciclovine-based imaging may play a role in castrate resistant states. Clinical comparison between PSMA- and fluciclovine-based imaging modalities in mCRPC and t-SCNC is warranted.

scholarly journals TBX2 Drives Neuroendocrine Prostate Cancer through Exosome-Mediated Repression of miR-200c-3p

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 5020
Author(s):  
Girijesh Kumar Patel ◽  
Sayanika Dutta ◽  
Mosharaf Mahmud Syed ◽  
Sabarish Ramachandran ◽  
Monica Sharma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Therapeutic Strategies ◽  
Signaling Mechanisms ◽  
Neuroendocrine Prostate Cancer ◽  
Signaling Axis ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Novel Therapeutic Strategies ◽  
Tbx2 Expression ◽  
Aggressive Subtype

Deciphering the mechanisms that drive transdifferentiation to neuroendocrine prostate cancer (NEPC) is crucial to identifying novel therapeutic strategies against this lethal and aggressive subtype of advanced prostate cancer (PCa). Further, the role played by exosomal microRNAs (miRs) in mediating signaling mechanisms that propagate the NEPC phenotype remains largely elusive. The unbiased differential miR expression profiling of human PCa cells genetically modulated for TBX2 expression led to the identification of miR-200c-3p. Our findings have unraveled the TBX2/miR-200c-3p/SOX2/N-MYC signaling axis in NEPC transdifferentiation. Mechanistically, we found that: (1) TBX2 binds to the promoter and represses the expression of miR-200c-3p, a miR reported to be lost in castrate resistant prostate cancer (CRPC), and (2) the repression of miR-200c-3p results in the increased expression of its targets SOX2 and N-MYC. In addition, the rescue of mir-200c-3p in the context of TBX2 blockade revealed that miR-200c-3p is the critical intermediary effector in TBX2 regulation of SOX2 and N-MYC. Further, our studies show that in addition to the intracellular mode, TBX2/miR-200c-3p/SOX2/N-MYC signaling can promote NEPC transdifferentiation via exosome-mediated intercellular mechanism, an increasingly recognized and key mode of propagation of the NEPC phenotype.

scholarly journals The expression of YAP1 is increased in high-grade prostatic adenocarcinoma but is reduced in neuroendocrine prostate cancer

2020 ◽  
Vol 23 (4) ◽  
pp. 661-669 ◽  
Author(s):  
Siyuan Cheng ◽  
Nestor Prieto-Dominguez ◽  
Shu Yang ◽  
Zachary M. Connelly ◽  
Samantha StPierre ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostatic Adenocarcinoma ◽  
High Grade ◽  
Neuroendocrine Prostate Cancer

Oct1 regulates cell growth of LNCaP cells and is a prognostic factor for prostate cancer

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factor ◽  
Hazard Analysis ◽  
Critical Role ◽  
Immunohistochemical Analysis ◽  
Lncap Cells ◽  
Cancer Specific Survival ◽  
High Gleason Score ◽  
Castrate Resistant ◽  
Transcription Factor 1

The androgen receptor (AR) plays a critical role in the development and the progression of prostate cancer. Alterations in theexpression of AR coregulators lead to AR hypersensitivity, which is one of the mechanisms underlying the progression ofprostate cancer into a castrate-resistant state. Octamer transcription factor 1 (Oct1) is a ubiquitous member of the POUhomeodomainfamily that functions as a coregulator of AR. In our study, the contribution of Oct1 to prostate cancerdevelopment was examined. Immunocytochemistry analysis showed that Oct1 is expressed in the nuclei of LNCaP cells.siRNA-mediated silencing of Oct1 expression inhibited LNCaP cell proliferation. Immunohistochemical analysis of Oct1expression in tumor specimens obtained from 102 patients with prostate cancer showed a positive correlation of Oct1immunoreactivity with a high Gleason score and AR immunoreactivity (p 5 0.0042 and p &lt; 0.0001, respectively). Moreover,patients with high immunoreactivity of Oct1 showed a low cancer-specific survival rate, and those patients with highimmunoreactivities of both Oct1 and AR exhibited poorer cancer-specific prognosis. Multivariate hazard analysis revealed asignificant correlation between high Oct1 immunoreactivity and poor cancer-specific survival (p 5 0.012). These resultsdemonstrate that Oct1 can be a prognostic factor in prostate cancer as a coregulator of AR and may lead to the developmentof a new therapeutic intervention for prostate cancer.

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