MicroRNA expressions associated with progression of prostate cancer cells to antiandrogen therapy resistance

Molecular Cancer

Research

Richard Ottman¹  Robert Lorch¹  Camha Nguyen¹  Ratna Chakrabarti¹ 

[1] Burnett School of Biomedical Sciences, University of Central Florida, Research Parkway, 12722, Orlando, Florida, USA;

关键词: MicroRNA;    Prostate cancer;    Antiandrogen;    Androgen deprivation;    Drug resistance;    Expression profiling;   

DOI  :  10.1186/1476-4598-13-1

 received in 2013-08-06, accepted in 2013-11-11,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundDevelopment of resistance to androgen deprivation therapy (ADT) is a major obstacle for the management of advanced prostate cancer. Therapies with androgen receptor (AR) antagonists and androgen withdrawal initially regress tumors but development of compensatory mechanisms including AR bypass signaling leads to re-growth of tumors. MicroRNAs (miRNAs) are small regulatory RNAs that are involved in maintenance of cell homeostasis but are often altered in tumor cells.ResultsIn this study, we determined the association of genome wide miRNA expression (1113 unique miRNAs) with development of resistance to ADT. We used androgen sensitive prostate cancer cells that progressed to ADT and AR antagonist Casodex (CDX) resistance upon androgen withdrawal and treatment with CDX. Validation of expression of a subset of 100 miRNAs led to identification of 43 miRNAs that are significantly altered during progression of cells to treatment resistance. We also show a correlation of altered expression of 10 proteins targeted by some of these miRNAs in these cells.ConclusionsWe conclude that dynamic alterations in miRNA expression occur early on during androgen deprivation therapy, and androgen receptor blockade. The cumulative effect of these altered miRNA expression profiles is the temporal modulation of multiple signaling pathways promoting survival and acquisition of resistance. These early events are driving the transition to castration resistance and cannot be studied in already developed CRPC cell lines or tissues. Furthermore our results can be used a prognostic marker of cancers with a potential to be resistant to ADT.

【 授权许可】

Unknown   
© Ottman et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.