Molecular Pathways Involved in Prostate Carcinogenesis: Insights from Public Microarray Datasets

Baetke, Sarah C.; Adriaens, Michiel E.; Seigneuric, Renaud; Evelo, Chris T.; Eijssen, Lars

doi:10.1371/journal.pone.0049831

Cited by 17 publications

(13 citation statements)

References 30 publications

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“…PCa is a heterogeneous–multifocal disease with a clinical outcome difficult to predict [14,15]. It is of great significance to identify novel diagnostic and prognostic markers to understand this multifaceted disease process [16-19]. An accurate and early diagnosis is essential for efficient management of PCa [20].…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of NUCB2 mRNA expression in prostate cancer

Zhang

et al. 2013

J Exp Clin Cancer Res

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BackgroundNucleobindin 2 (NUCB2) abnormal expression has been reported in gastric cancer and breast cancer. However, the role of NUCB2 in prostate cancer (PCa) remains unclear. The aim of the present study was to investigate the NUCB2 expression in PCa tissues and adjacent non-cancerous tissues and its potential relevance to clinicopathological variables and prognosis.MethodsNUCB2 mRNA expression was determined by real-time quantitative real time reverse transcriptase polymerase chain reaction in 180 pairs of fresh frozen PCa tissues and corresponding non-cancerous tissues. Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between NUCB2 expression and prognosis of PCa patients.ResultsOur results showed that the expression level of NUCB2 mRNA in PCa tissues was significantly higher than those in non-cancerous tissues. Our results indicated that the high expression of NUCB2 in PCa was associated with lymph node metastasis, preoperative PSA, Gleason score, and angiolymphatic invasion. Kaplan–Meier survival analysis showed that patients with high NUCB2 expression have shorter biochemical recurrence (BCR)-free survival time compared to patients with low NUCB2 expression. Multivariate analysis revealed that NUCB2 expression was an independent predictor of BCR-free survival.ConclusionsNUCB2 might play a positive role in PCa development and could serve as an independent predictor of BCR-free survival.

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Section: Discussionmentioning

confidence: 99%

Clinical significance of NUCB2 mRNA expression in prostate cancer

Zhang

et al. 2013

J Exp Clin Cancer Res

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“…Wallace et al have identified 17 different pathways that are altered in PCa 18. However, the molecular mechanisms governing the formation and progression of PCa are still not well understood 19,20. Of the many techniques to study PCa formation and development, prostaspheres produced from PCa cells grown suspended in a purified ECM gel/matrix in vitro2,16,21 or within a hanging drop2 represent the most commonly used systems in the field.…”

Section: Introductionmentioning

confidence: 99%

Sialylation facilitates self-assembly of 3D multicellular prostaspheres by using cyclo-RGDfK(TPP) peptide

Haq¹,

Samuel²,

Haxho³

et al. 2017

OTT

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BackgroundProstaspheres-based three dimensional (3D) culture models have provided insight into prostate cancer (PCa) biology, highlighting the importance of cell–cell interactions and the extracellular matrix (EMC) in the tumor microenvironment. Although these 3D classical spheroid platforms provide a significant advance over 2D models mimicking in vivo tumors, the limitations involve no control of assembly and structure with only limited spatial or glandular organization. Here, matrix-free prostaspheres from human metastatic prostate carcinoma PC3 and DU145 cell lines and their respective gemcitabine resistant (GemR) variants were generated by using cyclic Arg-Gly-Asp-D-Phe-Lys peptide modified with 4-carboxybutyl-triphenylphosphonium bromide (cyclo-RGDfK(TPP)).Materials and methodsMicroscopic imaging, immunocytochemistry (ICC), flow cytometry, sialidase, and WST-1 cell viability assays were used to evaluate the formation of multicellular tumor spheroid (MCTS), cell survival, morphologic changes, and expression levels of α2,6 and α2,3 sialic acid (SA) and E- and N-cadherin in DU145, PC3, and their GemR variants.ResultsBy using the cyclo-RGDfK(TPP) peptide platform in a dose- and time-dependent manner, both DU145 and DU145GemR cells formed small MCTS. In contrast, PC3 and PC3GemR cells formed irregular multicellular aggregates at all concentrations of cyclo-RGDfK(TPP) peptide, even after 6 days of incubation. ICC and flow cytometry results revealed that DU145 cells expressed higher amounts of E-cadherin but lower N-cadherin compared with PC3 cells. By using Maackia amurensis (α2,3-SA-specific MAL-II) and Sambucus nigra (α2,6-SA specific SNA) lectin-based cytochemistry staining and flow cytometry, it was found that DU145 and DU145GemR cells expressed 5 times more α2,6-SA than α2,3-SA on the cell surface. PC3 cells expressed 4 times more α2,3-SA than α2,6-SA, and the PC3GemR cells showed 1.4 times higher α2,6-SA than α2,3-SA. MCTS volume was dose-dependently reduced following pretreatment with α2,6-SA-specific neuraminidase (Vibrio cholerae). Oseltamivir phosphate enhanced cell aggregation and compaction of 3D MCTS formed with PC3 cells.ConclusionThe relative levels of specific sialoglycan structures on the cell surface correlate with the ability of PCa cells to form avascular multicellular prostaspheres.

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“…Human prostate carcinogenesis clearly involves disruption of multiple molecular and biological processes, which contribute to its heterogeneity as a clinical entity (2). Normal prostate development, growth, and function, as well as the emergence of prostate cancer are androgen-dependent processes (3).…”

Section: Introductionmentioning

confidence: 99%

Dietary Tomato and Lycopene Impact Androgen Signaling- and Carcinogenesis-Related Gene Expression during Early TRAMP Prostate Carcinogenesis

Wan

Tan

Thomas‐Ahner

et al. 2014

Cancer Prevention Research

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Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4-10 wk-of-age. Eight-week-old mice underwent sham surgery, castration, or castration followed by testosterone-repletion (2.5 mg/kg/d initiated 1 wk after castration). Ten-wk-old intact TRAMP mice exhibit early multifocal prostatic intraepithelial neoplasia (PIN). Of the 200 prostate cancer-related genes measured by quantitative NanoString®, 189 are detectable, 164 significantly differ by genotype, 179 by testosterone status, and 30 by diet type (P<0.05). In TRAMP, expression of Birc5, Mki67, Aurkb, Ccnb2, Foxm1, and Ccne2 is greater compared to WT and is decreased by castration. In parallel, castration reduces Ki67-positive staining (P<0.0001) compared to intact and testosterone-repleted TRAMP mice. Expression of genes involved in androgen metabolism/signaling pathways are reduced by lycopene feeding (Srd5a1) and by tomato-feeding (Srd5a2, Pxn, and Srebf1). Additionally, tomato-feeding significantly reduced expression of genes associated with stem cell features, Aldh1a and Ly6a, while lycopene-feeding significantly reduced expression of neuroendocrine differentiation-related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early stages of prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk.

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Molecular Pathways Involved in Prostate Carcinogenesis: Insights from Public Microarray Datasets

Cited by 17 publications

References 30 publications

Clinical significance of NUCB2 mRNA expression in prostate cancer

Clinical significance of NUCB2 mRNA expression in prostate cancer

Sialylation facilitates self-assembly of 3D multicellular prostaspheres by using cyclo-RGDfK(TPP) peptide

Dietary Tomato and Lycopene Impact Androgen Signaling- and Carcinogenesis-Related Gene Expression during Early TRAMP Prostate Carcinogenesis

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