LINE-1 ORF-1p functions as a novel androgen receptor co-activator and promotes the growth of human prostatic carcinoma cells
| Autor: | Fan Zhang, Yutao Yang, Fan Feng, Yunfeng Zhu, Yongping Yang, Jianhui Qv, Chunping Wang, Yinying Lu, Chuanfu Zhang, Xudong Gao, Zhong-Xian Xu, Jiajun Cui, Zhen Zeng |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Cytoplasm Transcription Genetic medicine.drug_class Androgen receptor signaling pathway Gene Expression Biology Ligands Open Reading Frames Cell Line Tumor Protein Interaction Mapping LNCaP medicine Transcriptional regulation Humans Phosphorylation RNA Small Interfering Promoter Regions Genetic Cell Proliferation Cell Nucleus RNF4 Prostatic Neoplasms Cell Biology Metribolone Prostate-Specific Antigen Androgen Molecular biology Androgen receptor HEK293 Cells Long Interspersed Nucleotide Elements Receptors Androgen Cancer research RNA Interference Signal transduction Androgen Response Element Protein Binding Signal Transduction |
| Zdroj: | Cellular Signalling. 25:479-489 |
| ISSN: | 0898-6568 |
| DOI: | 10.1016/j.cellsig.2012.11.004 |
| Popis: | Widespread interest in the mechanism of transcriptional regulation by the androgen receptor (AR) has been stimulated by the finding that AR signaling is critically important in the progression of human prostate cancers. Co-factors, the co-repressors, or the co-activators are responsible for the regulation of AR activation. The pro-oncogene human Long Interspersed Nucleotide acid Element-1 (LINE-1) encodes LINE-1 ORF-1p and plays important roles in the development and progression of several human carcinomas. In this study, the results showed that LINE-1 ORF-1p increased the AR transcriptional activity and in turn enhanced the expression of prostate specific antigen (PSA) in the presence of R1881. A physical protein-protein interaction between the AR signaling and the LINE-1 ORF-1p was identified by the immunoprecipitation assays and GST pull-down assays. Furthermore, LINE-1 ORF-1p would function as a novel AR positive co-regulator through modulating its cytoplasm/nucleus translocation and the recruitment to the androgen response element in the PSA gene promoter. Our date also showed that the LINE-1 ORF-1p promoted the proliferation and anchor-independent growth of LNCaP (ligand dependent) and PC-3 (ligand independent) human prostatic carcinoma cells. By investigating a novel role of the LINE-1 ORF-1p in the androgen/androgen receptor signaling pathway regulation, our study identifies that LINE-1 ORF-1p may be a novel AR co-regulator and molecular target for human prostate carcinoma therapy. |
| Databáze: | OpenAIRE |
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