Genomic analyses of the metastasis‐derived prostate cancer cell lines LNCaP, VCaP, and PC3‐AR

The Prostate ◽  
2021 ◽  
Author(s):  
Karolina Sienkiewicz ◽  
Chunsong Yang ◽  
Bryce M. Paschal ◽  
Aakrosh Ratan
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Prostate Cancer Cell Lines ◽  
Genomic Analyses

scholarly journals Genomic Analyses of the Metastasis-derived LNCaP, VCaP, and PC3-AR Prostate Cancer Cell Lines

2021 ◽  
Author(s):  
Karolina Sienkiewicz ◽  
Chunsong Yang ◽  
Bryce M. Paschal ◽  
Aakrosh Ratan
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
P53 Protein ◽  
Cancer Cell Lines ◽  
Lncap Cells ◽  
Prostate Cancer Cell Lines ◽  
Biological Studies ◽  
Genomic Analyses

The lymph node metastasis-derived LNCaP, the bone metastasis-derived PC3 (skull), and VCaP (vertebral) cell lines are widely used preclinical models of human prostate cancer (CaP) and have been described in >19,000 publications. Here, we report on short-read whole-genome sequencing and genomic analyses of LNCaP, VCaP, and PC3 cells stably transduced with WT AR (PC3-AR) . LNCaP cells are composed of multiple subpopulations, which results in non-integral copy number states and a high mutational load when the data is analyzed in bulk. All three cell lines contain pathogenic mutations and homozygous deletions in genes involved in DNA mismatch repair, along with deleterious mutations in cell-cycle, Wnt signaling, and other cellular processes. Furthermore, LNCaP cells contain a missense mutation in a well-known CaP hotspot of TP53, whereas both PC3-AR and VCaP have truncating mutations in TP53 and do not express p53 protein. In addition, we detect the signatures of chromothripsis of the q arms of chromosome 5 in both PC3-AR and VCaP cells, strengthening the association of TP53 inactivation with chromothripsis reported in other systems. Our work provides a resource for genetic, genomic, and biological studies employing these commonly-used prostate cancer cell lines.

797: Noggin Blocks the Osteoinductive Properties of Human Prostate Cancer Cell Lines

2006 ◽  
Vol 175 (4S) ◽  
pp. 258-258
Author(s):  
Ruth Schwaninger ◽  
Cyrill A. Rentsch ◽  
Antoinette Wetterwald ◽  
Irena Klima ◽  
Gabri Van der Pluijm ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Human Prostate Cancer Cell ◽  
Prostate Cancer Cell Lines

Expression of Urokinase and Its Receptor in Invasive and Non-Invasive Prostate Cancer Cell Lines

1992 ◽  
Vol 68 (06) ◽  
pp. 662-666 ◽  
Author(s):  
W Hollas ◽  
N Hoosein ◽  
L W K Chung ◽  
A Mazar ◽  
J Henkin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Steady State ◽  
Cell Surface ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Lncap Cells ◽  
Prostate Cancer Cell Lines ◽  
Non Invasive

SummaryWe previously reported that extracellular matrix invasion by the prostate cancer cell lines, PC-3 and DU-145 was contingent on endogenous urokinase being bound to a specific cell surface receptor. The present study was undertaken to characterize the expression of both urokinase and its receptor in the non-invasive LNCaP and the invasive PC-3 and DU-145 prostate cells. Northern blotting indicated that the invasive PC-3 cells, which secreted 10 times more urokinase (680 ng/ml per 106 cells per 48 h) than DU-145 cells (63 ng/ml per 106 cells per 48 h), had the most abundant transcript for the plasminogen activator. This, at least, partly reflected a 3 fold amplification of the urokinase gene in the PC-3 cells. In contrast, urokinase-specific transcript could not be detected in the non-invasive LNCaP cells previously characterized as being negative for urokinase protein. Southern blotting indicated that this was not a consequence of deletion of the urokinase gene. Crosslinking of radiolabelled aminoterminal fragment of urokinase to the cell surface indicated the presence of a 51 kDa receptor in extracts of the invasive PC-3 and DU-145 cells but not in extracts of the non-invasive LNCaP cells. The amount of binding protein correlated well with binding capacities calculated by Scatchard analysis. In contrast, the steady state level of urokinase receptor transcript was a poor predictor of receptor display. PC-3 cells, which were equipped with 25,000 receptors per cell had 2.5 fold more steady state transcript than DU-145 cells which displayed 93,000 binding sites per cell.

Synthesis, Anticancer Activity on Prostate Cancer Cell Lines and Molecular Modeling Studies of Flurbiprofen-Thioether Derivatives as Potential Target of MetAP (Type II)

2020 ◽  
Vol 16 (6) ◽  
pp. 735-749 ◽  
Author(s):  
Özgür Yılmaz ◽  
Burak Bayer ◽  
Hatice Bekçi ◽  
Abdullahi I. Uba ◽  
Ahmet Cumaoğlu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Modeling ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Prostate Cancer Cell Lines ◽  
Molecular Modeling Studies

Background:: Prostate cancer is still one of the serious causes of mortality and morbidity in men. Despite recent advances in anticancer therapy, there is a still need of novel agents with more efficacy and specificity in the treatment of prostate cancer. Because of its function on angiogenesis and overexpression in the prostate cancer, methionine aminopeptidase-2 (MetAP-2) has been a potential target for novel drug design recently. Objective:: A novel series of Flurbiprofen derivatives N-(substituted)-2-(2-(2-fluoro-[1,1'- biphenyl]-4-il)propanoyl)hydrazinocarbothioamide (3a-c), 4-substituted-3-(1-(2-fluoro-[1,1'-biphenyl]- 4-yl)ethyl)-1H-1,2,4-triazole-5(4H)-thione (4a-d), 3-(substitutedthio)-4-(substituted-phenyl)- 5-(1-(2-fluoro-[1,1'-biphenyl]-4-yl)ethyl)-4H-1,2,4-triazole (5a-y) were synthesized. The purpose of the research was to evaluate these derivatives against MetAP-2 in vitro and in silico to obtain novel specific and effective anticancer agents against prostate cancer. Methods: The chemical structures and purities of the compounds were defined by spectral methods (1H-NMR, 13C-NMR, HR-MS and FT-IR) and elemental analysis. Anticancer activities of the compounds were evaluated in vitro by using MTS method against PC-3 and DU-143 (androgenindependent human prostate cancer cell lines) and LNCaP (androgen-sensitive human prostate adenocarcinoma) prostate cancer cell lines. Cisplatin was used as a positive sensitivity reference standard. Results:: Compounds 5b and 5u; 3c, 5b and 5y; 4d and 5o showed the most potent biological activity against PC3 cancer cell line (IC50= 27.1 μM, and 5.12 μM, respectively), DU-145 cancer cell line (IC50= 11.55 μM, 6.9 μM and 9.54 μM, respectively) and LNCaP cancer cell line (IC50= 11.45 μM and 26.91 μM, respectively). Some compounds were evaluated for their apoptotic caspases protein expression (EGFR/PI3K/AKT pathway) by Western blot analysis in androgen independent- PC3 cells. BAX, caspase 9, caspsase 3 and anti-apoptotic BcL-2 mRNA levels of some compounds were also investigated. In addition, molecular modeling studies of the compounds on MetAP-2 enzyme active site were evaluated in order to get insight into binding mode and energy. Conclusion:: A series of Flurbiprofen-thioether derivatives were synthesized. This study presented that some of the synthesized compounds have remarkable anticancer and apoptotic activities against prostate cancer cells. Also, molecular modeling studies exhibited that there is a correlation between molecular modeling and anticancer activity results.

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