Evaluation of Docetaxel-Sensitive and Docetaxel-Resistant Proteomes in PC-3 Cells

2015 ◽  
Vol 95 (1) ◽  
pp. 114-119 ◽  
Author(s):  
Shulu Zu ◽  
Weiming Ma ◽  
Pan Xiao ◽  
Yazhou Cui ◽  
Tianjia Ma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Polyacrylamide Gel Electrophoresis ◽  
Acquired Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Ionization Time ◽  
Flight Mass Spectrometry ◽  
Docetaxel Resistance ◽  
Castration Resistant ◽  
Glucose Regulated Protein

Objectives: Docetaxel was the first drug with proven survival benefit in men with castration-resistant prostate cancer. Acquired resistance to docetaxel precedes fatality in castration-resistant prostate cancer. The aims of this study were to evaluate docetaxel-sensitive and docetaxel-resistant proteomes in PC-3 cells, and to investigate the molecular mechanism of docetaxel-resistant PC-3 cells. Methods: Docetaxel-resistant PC-3 cells were developed by docetaxel dose escalation. The global profiling of the protein expression was investigated in docetaxel-sensitive and docetaxel-resistant proteomes in PC-3 cells using 2-dimensional polyacrylamide gel electrophoresis/matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results: Forty-nine differential proteins were found in docetaxel-resistant PC-3 cells in comparison with docetaxel-sensitive PC-3 cells. Expression in 29 proteins was upregulated, whereas expression in 20 proteins was downregulated. ATP synthase and galectin-1 were involved in the formation of tumor vessels; calreticulin, cathepsin D, and cofilin were involved in tumor metastasis, and GRP78 (78-kDa glucose-regulated protein) and microtubule-associated protein-6 were involved in drug resistance of tumor. Conclusion: It is suggested that a proteomic expression difference exists between docetaxel-sensitive and docetaxel-resistant PC-3 cells, which would be helpful for further understanding the molecular mechanisms of docetaxel resistance in PC-3 cells.

scholarly journals Identification of Key Genes and Molecular Mechanisms Associated With Docetaxel Resistance in Castration Resistant Prostate Cancer Based on Bioinformatics Analysis

2020 ◽  
Author(s):  
Yu Liu ◽  
Changpeng Hu ◽  
Qian Zhang ◽  
Wuyi Liu ◽  
Guobing Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Castration Resistant Prostate Cancer ◽  
Mesenchymal Transition ◽  
Docetaxel Resistance ◽  
Castration Resistant ◽  
E2f Transcription Factor ◽  
Key Genes

Abstract BackgroundCastration resistant prostate cancer (CRPC) is one of the most common solid tumor with high mortality and limited therapeutic options, and docetaxel is the first-line chemotherapy for patients. However, the long-term use of docetaxel has limited its clinical applications. The aim of this study was to identify docetaxel-resistant key genes and molecular mechanisms. ResultsTUBB4A (Class IVa beta-tubulin), SRPX (Sushi repeat containing protein, X chromosome) and CSRP2 (Cysteine and glycine rich protein 2) were finally identified as the key genes tightly related to docetaxel resistance. TUBB4A and CSRP2 may participate in docetaxel resistance by E2F transcription factor and MYC proto-Oncogene in the process of cell cycle, and SRPX may participate in docetaxel resistance by epithelial–mesenchymal transition (EMT) and P53 pathway. ConclusionTUBB4A, SRPX and CSRP2 may be the key genes associated with docetaxel resistance, which could be prognostic biomarkers for docetaxel resistance in CRPC.

Expression pattern of androgen receptors, AR-V7 and AR-567es, in circulating tumor cells and paired plasma-derived extracellular vesicles in metastatic castration resistant prostate cancer

The Analyst ◽  
2019 ◽  
Vol 144 (22) ◽  
pp. 6671-6680 ◽  
Author(s):  
Areti Strati ◽  
Martha Zavridou ◽  
Evangelos Bournakis ◽  
Sophia Mastoraki ◽  
Evi Lianidou
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Androgen Receptors ◽  
Acquired Resistance ◽  
Predictive Biomarker ◽  
Castration Resistant Prostate Cancer ◽  
Androgen Receptor Signaling ◽  
Castration Resistant ◽  
Signaling Inhibitors ◽  
Androgen Receptor Splice Variant

Androgen-receptor splice variant 7 (AR-V7) is a highly promising liquid biopsy predictive biomarker showing primary or acquired resistance to novel androgen receptor signaling inhibitors in metastatic castration resistant prostate cancer (mCRPC).

EGFR mediates docetaxel resistance in human castration-resistant prostate cancer through the Akt-dependent expression of ABCB1 (MDR1)

2014 ◽  
Vol 89 (4) ◽  
pp. 591-605 ◽  
Author(s):  
Tzyh-Chyuan Hour ◽  
Shiu-Dong Chung ◽  
Wang-Yi Kang ◽  
Ying-Chu Lin ◽  
Shu-Ju Chuang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Docetaxel Resistance ◽  
Castration Resistant

scholarly journals Identification of Docetaxel Resistance Genes in Castration-Resistant Prostate Cancer

2011 ◽  
Vol 11 (2) ◽  
pp. 329-339 ◽  
Author(s):  
Mercedes Marín-Aguilera ◽  
Jordi Codony-Servat ◽  
Susana G. Kalko ◽  
Pedro L. Fernández ◽  
Raquel Bermudo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Resistance Genes ◽  
Castration Resistant Prostate Cancer ◽  
Docetaxel Resistance ◽  
Castration Resistant

TACC2 Is an Androgen-Responsive Cell Cycle Regulator Promoting Androgen-Mediated and Castration-Resistant Growth of Prostate Cancer

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Survival Rates ◽  
Tumor Formation ◽  
Castration Resistant Prostate Cancer ◽  
Cellular Models ◽  
Castration Resistant ◽  
Hormone Refractory ◽  
Immunocompromised Mice

Despite the existence of effective antiandrogen therapy for prostate cancer, the disease oftenprogresses to castration-resistant states. Elucidation of the molecular mechanisms underlying theresistance for androgen deprivation in terms of the androgen receptor (AR)-regulated pathwaysis a requisite to manage castration-resistant prostate cancer (CRPC). Using a ChIP-cloning strategy,we identified functional AR binding sites (ARBS) in the genome of prostate cancer cells. Wediscovered that a centrosome- and microtubule-interacting gene, transforming acidic coiled-coilprotein 2 (TACC2), is a novel androgen-regulated gene.Weidentified a functional AR-binding site(ARBS) including two canonical androgen response elements in the vicinity of TACC2 gene, inwhich activated hallmarks of histone modification were observed. Androgen-dependent TACC2induction is regulated by AR, as confirmed by AR knockdown or its pharmacological inhibitorbicalutamide. Using long-term androgen-deprived cells as cellular models of CRPC, we demonstratedthat TACC2 is highly expressed and contributes to hormone-refractory proliferation, assmall interfering RNA-mediated knockdown of TACC2 reduced cell growth and cell cycle progression.By contrast, in TACC2-overexpressing cells, an acceleration of the cell cycle was observed. Invivo tumor formation study of prostate cancer in castrated immunocompromised mice revealedthat TACC2 is a tumor-promoting factor. Notably, the clinical significance of TACC2 was demonstratedby a correlation between high TACC2 expression and poor survival rates. Taken togetherwith the critical roles of TACC2 in the cell cycle and the biology of prostate cancer, we infer thatthe molecule is a potential therapeutic target in CRPC

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