Document Detail


Androgen receptor regulates CD168 expression and signaling in prostate cancer.
MedLine Citation:
PMID:  18174258     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Dysregulation of the androgen receptor (AR) and its signaling in the prostate often occurs during normal aging or after androgen ablation, consequently leading to the development of hormone-refractory prostate cancer (HRPC). Hyaluronan (HA) plays an important role in this transformation of androgen-independent cancer. Previous studies have shown that activation of the receptor for hyaluronan-mediated motility, CD168, was correlated with the Gleason's score, cancer stage, transformation and metastasis in >90% of HRPC patients. However, the relationship between loss of AR dependency and HA-mediated CD168 signaling remains unclear. We report here that AR regulates normal CD168 expression and its downstream signaling in androgen-dependent (AD) prostatic epithelial cell lines. Furthermore, we observed that the concurrent treatments of HA and dihydrotestosterone (DHT), a native androgen, significantly promoted the tumorigenicity of AD prostate cancer cell lines, which showed elevated rates of cell proliferation, invasion and metastasis to the human bone marrow endothelial cell layer. Inhibition of CD168 downstream Rho-activated protein kinases completely prevented this type of tumorigenicity. These findings suggest that the interaction of androgen and AR is essential for regulating HA-mediated cancer progression via the CD168/ROCK signal transduction pathway and also indicate that the loss of AR regulation not only causes CD168 overexpression but it also activates HA-mediated CD168 signaling in malignant cancer progression and metastasis of HRPC.
Authors:
Shi-Lung Lin; Donald Chang; Angela Chiang; Shao-Yao Ying
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-01-03
Journal Detail:
Title:  Carcinogenesis     Volume:  29     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-03-03     Completed Date:  2008-03-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  282-90     Citation Subset:  IM    
Affiliation:
Department of Cell and Neurobiology, Keck School of Medicine, BMT-403, University of Southern California, 1333 San Pablo Street, Los Angeles, CA 90033, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD44 / biosynthesis*,  physiology*
Bone Marrow Cells / metabolism
Cell Line, Tumor
Dihydrotestosterone / pharmacology
Extracellular Matrix Proteins / biosynthesis*,  physiology*
Gene Expression Regulation, Neoplastic*
Humans
Male
Mice
Mice, Inbred BALB C
Neoplasm Invasiveness
Neoplasm Metastasis
Prostatic Neoplasms / metabolism*
Receptors, Androgen / physiology*
Signal Transduction
Grant Support
ID/Acronym/Agency:
CA-85722/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD44; 0/Extracellular Matrix Proteins; 0/Receptors, Androgen; 0/hyaluronan-mediated motility receptor; 521-18-6/Dihydrotestosterone

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