title: LINE-1 ORF-1p functions as a novel androgen receptor co-activator and promotes the growth of human prostatic carcinoma cells.
abstract: 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.
authors.affiliation: Center of Therapeutic Research for Hepatocellular Carcinoma, 302 Military Hospital Beijing 100039, PR China.
authors.forename: Yinying
authors.initials: Y
authors.lastname: Lu
authors.forename: Fan
authors.initials: F
authors.lastname: Feng
authors.forename: Yutao
authors.initials: Y
authors.lastname: Yang
authors.forename: Xudong
authors.initials: X
authors.lastname: Gao
authors.forename: Jiajun
authors.initials: J
authors.lastname: Cui
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Zhang
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Zhongxian
authors.initials: Z
authors.lastname: Xu
authors.forename: Jianhui
authors.initials: J
authors.lastname: Qv
authors.forename: Chunping
authors.initials: C
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zeng
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yongping
authors.initials: Y
authors.lastname: Yang
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D016366:Open Reading Frames / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D025941:Protein Interaction Mapping; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D008024:Ligands; D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D015741:Metribolone; D017430:Prostate-Specific Antigen