| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Li, Tiantian Chen, Shaoyong Kantoff, Philip W. Wang, Xiaodong Hsieh, Chen-lin Sun, Tong Lee, Gwo-shu Mary Fei, Teng Brown, Myles Chen, Yiwen Balk, Steven P. Sweeney, Christopher J. Liu, Xiaole Shirley Gao, Yanfei |
| Description |
Author Affiliation: Hsieh CL ( Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115); Fei T ( Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115); Chen Y ( Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215); Li T ( Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115); Gao Y ( Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.); Wang X ( Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115); Sun T ( Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115); Sweeney CJ ( Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115); Lee GS ( Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115); Chen S ( Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.); Balk SP ( Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.); Liu XS ( Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215); Brown M ( Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115); Kantoff PW ( Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115); |
| Abstract |
The androgen receptor (AR) is a key factor that regulates the behavior and fate of prostate cancer cells. The AR-regulated network is activated when AR binds enhancer elements and modulates specific enhancer-promoter looping. Kallikrein-related peptidase 3 (KLK3), which codes for prostate-specific antigen (PSA), is a well-known AR-regulated gene and its upstream enhancers produce bidirectional enhancer RNAs (eRNAs), termed KLK3e. Here, we demonstrate that KLK3e facilitates the spatial interaction of the KLK3 enhancer and the KLK2 promoter and enhances long-distance KLK2 transcriptional activation. KLK3e carries the core enhancer element derived from the androgen response element III (ARE III), which is required for the interaction of AR and Mediator 1 (Med1). Furthermore, we show that KLK3e processes RNA-dependent enhancer activity depending on the integrity of core enhancer elements. The transcription of KLK3e was detectable and its expression is significantly correlated with KLK3 (R(2) = 0.6213, P < 5 × 10(-11)) and KLK2 (R(2) = 0.5893, P < 5 × 10(-10)) in human prostate tissues. Interestingly, RNAi silencing of KLK3e resulted in a modest negative effect on prostate cancer cell proliferation. Accordingly, we report that an androgen-induced eRNA scaffolds the AR-associated protein complex that modulates chromosomal architecture and selectively enhances AR-dependent gene expression. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
20 |
| Volume Number |
111 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2014-05-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Enhancer Elements, Genetic Gene Expression Regulation, Neoplastic Prostatic Neoplasms Metabolism Receptors, Androgen Animals COS Cells Cell Line, Tumor Cercopithecus Aethiops Gene Silencing Kallikreins Mediator Complex Subunit 1 Promoter Regions, Genetic Prostate Prostate-Specific Antigen RNA Interference Regulatory Sequences, Nucleic Acid Tissue Kallikreins Transcription, Genetic Transcriptional Activation Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
