Gene Expression Profiling of Prostate Cancer–Associated Genes Identifies Fibromodulin as Potential Novel Biomarker for Prostate Cancer

Background The aim of this study was to evaluate the gene expression profiles of a set of prostate cancer–associated genes in prostate cancer cell lines, to determine their association with different cancer phenotypes and identify potential novel biomarkers for this disease. Methods Quantitative real-time PCR was used to determine the expression profiles of 21 prostate cancer–associated genes in the human prostate cancer cell lines PC-3 and LNCaP, using the nontumorigenic cell line PWR-1E as control cell line. Genes evaluated were ESM-1, SERPINE2, CLU, BGN, A2M, PENK, FMOD, CD81, DCN, TSPAN8, KBTBD10, F2RL1, TMSB4X, SNCG, CXXC5, FOXQ1, PDPN, SPN, CAV1, CD24 and KLK3. A potential biomarker from this set of genes, the FMOD gene, encoding the small leucine-rich proteoglycan fibromodulin, was selected for further evaluation in clinical samples from patients diagnosed with benign or malignant prostatic disease. Results Several of the evaluated genes showed significantly altered expression in the prostate cancer cell lines, compared with nontumorigenic PWR-1E cells. Further evaluation of FMOD transcript in prostate clinical samples from patients diagnosed with benign or malignant prostatic disease identified a significant difference in the expression levels of this proteoglycan between benign and malignant tissue (p<0.05). Conclusions A number of gene transcripts were differentially expressed by the cell lines assayed. Among them, FMOD was further evaluated in clinical samples and was found to be differentially expressed between benign and prostate cancer tissue. Further validation of FMOD transcript in a larger population is required to ascertain its usefulness as biomarker for prostate cancer.

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Gene Expression Profiles of Prostate Cancer Cell Lines, LNCaP, PC-3 and DU-145, Assessed by cDNA Microarray

The Kitakanto Medical Journal ◽

10.2974/kmj.58.363 ◽

2008 ◽

Vol 58 (4) ◽

pp. 363-369 ◽

Cited By ~ 2

Author(s):

Keigo Okamura ◽

Hidekazu Koike ◽

Hiroshi Matsui ◽

Kazuhiro Suzuki

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cdna Microarray ◽

Prostate Cancer Cell ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Cancer Cell Lines ◽

Prostate Cancer Cell Lines

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

Medicinal Chemistry ◽

10.2174/1573406415666190613162322 ◽

2020 ◽

Vol 16 (6) ◽

pp. 735-749 ◽

Cited By ~ 1

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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Enzalutamide response in a panel of prostate cancer cell lines reveals a role for glucocorticoid receptor in enzalutamide resistant disease

Scientific Reports ◽

10.1038/s41598-020-78798-x ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Rebecca Smith ◽

Moqing Liu ◽

Tiera Liby ◽

Nora Bayani ◽

Elmar Bucher ◽

...

Keyword(s):

Prostate Cancer ◽

Glucocorticoid Receptor ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Lines ◽

Response To Therapy ◽

Model Systems ◽

Prostate Cancer Cell Lines

AbstractRepresentative in vitro model systems that accurately model response to therapy and allow the identification of new targets are important for improving our treatment of prostate cancer. Here we describe molecular characterization and drug testing in a panel of 20 prostate cancer cell lines. The cell lines cluster into distinct subsets based on RNA expression, which is largely driven by functional Androgen Receptor (AR) expression. KLK3, the AR-responsive gene that encodes prostate specific antigen, shows the greatest variability in expression across the cell line panel. Other common prostate cancer associated genes such as TMPRSS2 and ERG show similar expression patterns. Copy number analysis demonstrates that many of the most commonly gained (including regions containing TERC and MYC) and lost regions (including regions containing TP53 and PTEN) that were identified in patient samples by the TCGA are mirrored in the prostate cancer cell lines. Assessment of response to the anti-androgen enzalutamide shows a distinct separation of responders and non-responders, predominantly related to status of wild-type AR. Surprisingly, several AR-null lines responded to enzalutamide. These AR-null, enzalutamide-responsive cells were characterized by high levels of expression of glucocorticoid receptor (GR) encoded by NR3C1. Treatment of these cells with the anti-GR agent mifepristone showed that they were more sensitive to this drug than enzalutamide, as were several of the enzalutamide non-responsive lines. This is consistent with several recent reports that suggest that GR expression is an alternative signaling mechanism that can bypass AR blockade. This study reinforces the utility of large cell line panels for the study of cancer and identifies several cell lines that represent ideal models to study AR-null cells that have upregulated GR to sustain growth.

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