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 ◽  
...  
2015 ◽  
Vol 95 (1) ◽  
pp. 114-119 ◽  
Author(s):  
Shulu Zu ◽  
Weiming Ma ◽  
Pan Xiao ◽  
Yazhou Cui ◽  
Tianjia Ma ◽  
...  

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.


2011 ◽  
Vol 11 (2) ◽  
pp. 329-339 ◽  
Author(s):  
Mercedes Marín-Aguilera ◽  
Jordi Codony-Servat ◽  
Susana G. Kalko ◽  
Pedro L. Fernández ◽  
Raquel Bermudo ◽  
...  

The Prostate ◽  
2012 ◽  
Vol 73 (5) ◽  
pp. 512-521 ◽  
Author(s):  
Jordi Codony-Servat ◽  
Mercedes Marín-Aguilera ◽  
Laura Visa ◽  
Xabier García-Albéniz ◽  
Estela Pineda ◽  
...  

2016 ◽  
Vol 70 (5) ◽  
pp. 709-713 ◽  
Author(s):  
Òscar Reig ◽  
Mercedes Marín-Aguilera ◽  
Gemma Carrera ◽  
Natalia Jiménez ◽  
Laia Paré ◽  
...  

2017 ◽  
Vol 72 (2) ◽  
pp. e49
Author(s):  
Òscar Reig ◽  
Mercedes Marín-Aguilera ◽  
Gemma Carrera ◽  
Natalia Jiménez ◽  
Laia Paré ◽  
...  

2020 ◽  
Author(s):  
Yu Liu ◽  
Changpeng Hu ◽  
Qian Zhang ◽  
Wuyi Liu ◽  
Guobing Li ◽  
...  

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.


2017 ◽  
Vol 14 (2) ◽  
pp. 1748-1756 ◽  
Author(s):  
Yun-Fei Li ◽  
Hui-Hua Ji ◽  
Zheng-Long Zhang ◽  
Tao-Tao Zhang ◽  
Wei Gan ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuting Shan ◽  
Yingbo Huang ◽  
Adam M. Lee ◽  
Joshua Mentzer ◽  
Alexander Ling ◽  
...  

While functional studies of long noncoding RNAs (lncRNAs) have mostly focused on how they influence disease diagnosis and prognosis, the pharmacogenomic relevance of lncRNAs remains largely unknown. Here, we test the hypothesis that the expression of a lncRNA, grow arrest-specific 5 (GAS5) can be a biomarker for docetaxel response in castration resistant prostate cancer (CRPC) using both prostate cancer (PCa) cell lines and CRPC patient datasets. Our results suggest that lower GAS5 expression is associated with docetaxel resistance in both PCa cell lines and CRPC patients. Further experiments also suggest that GAS5 is downregulated in docetaxel resistant CRPC cell lines, which reinforces its potential as a biomarker for docetaxel response. To examine the underlying biological mechanisms, we transiently knockdown GAS5 expression in PCa cell lines and then subject the cells to docetaxel treatment overtime. We did not observe a decrease in docetaxel induced growth inhibition or apoptosis in the siRNA treated cells. The findings suggest that there is no direct causal relationship between change in GAS5 expression and docetaxel response. Subsequently, we explored the indirect regulation among GAS5, ATP binding cassette subfamily B member 1 (ABCB1), and docetaxel sensitivity. We showed that transient knockdown GAS5 did not lead to significant changes in ABCB1 expression. Therefore, we rule out the hypothesis that GAS5 directly down regulate ABCB1 that lead to docetaxel sensitivity. In conclusion, our work suggests that GAS5 can serve as a predictive biomarker for docetaxel response in CRPC; however, the exact mechanism behind the observed correlation remain to be elucidated.


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