Document Detail


The differential effects of prostate stromal cells derived from different zones on prostate cancer epithelial cells under the action of sex hormones.
MedLine Citation:
PMID:  21765438     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It is well known that prostate cancer (PCa) occurs predominantly in the peripheral zone (PZ), whereas benign prostatic hyperplasia (BPH) typically develops in the transition zone. To identify possible mechanisms underlying zonal differences, we compared the effects of prostate stromal cells derived from the peripheral zone (PZsc) and the transition zone (TZsc) on a PCa epithelial cell line (PC3) in the presence of sex hormones. First, we observed that androgen receptor (AR) mRNA was more highly expressed in PZsc than TZsc when the cells were treated with dihydrotestosterone (DHT) and β-oestradiol (E2) (P<0.05). By ELISA, we looked for differences in the secretion of peptide growth factors from PZsc and TZsc. We found that keratinocyte growth factor (KGF) secretion increased with increasing concentrations of DHT (P<0.01) and was higher in PZsc than TZsc. Under treatment with DHT plus E2, PZsc secreted more transforming growth factor-β1 (TGF-β1) than TZsc, but this pattern was reversed when the cells were treated with E2 only. With increasing concentrations of DHT, insulin-like growth factor-1 (IGF-1) secretion increased in PZsc but decreased in TZsc. To further characterize the effects of PZsc and TZsc on PC3 cells, we developed a coculture model and performed MTT assays, Western blot analysis and real-time RT-PCR. We found that PZsc promoted PC3 cell proliferation and progression better than TZsc, particularly when treated with 10 nmol l(-1) DHT plus 10 nmol l(-1) E2. In conclusion, our data suggest that PZsc may have a greater capacity to induce PCa development and progression than TZsc via growth factors regulated by sex hormones. These findings provide possible mechanisms underlying zonal differences in prostate diseases, which may aid the search for novel therapeutic targets for PCa.
Authors:
Qi Jiang; Bang-Min Han; Fu-Jun Zhao; Yan Hong; Shu-Jie Xia
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-07-18
Journal Detail:
Title:  Asian journal of andrology     Volume:  13     ISSN:  1745-7262     ISO Abbreviation:  Asian J. Androl.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-07     Completed Date:  2012-02-27     Revised Date:  2013-09-17    
Medline Journal Info:
Nlm Unique ID:  100942132     Medline TA:  Asian J Androl     Country:  China    
Other Details:
Languages:  eng     Pagination:  798-805     Citation Subset:  IM    
Affiliation:
Department of Urology, Shanghai First People's Hospital, Institute of Urology, Shanghai Jiao Tong University, Shanghai 200080, China.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Blotting, Western
Cell Proliferation
Coculture Techniques
DNA Primers
Enzyme-Linked Immunosorbent Assay
Gonadal Steroid Hormones / genetics,  physiology*
Growth Substances / physiology
Humans
Male
Proliferating Cell Nuclear Antigen / metabolism
Prostate / cytology*
Prostatic Neoplasms / pathology*,  physiopathology
Proto-Oncogene Proteins c-bcl-2 / metabolism
Real-Time Polymerase Chain Reaction
Stromal Cells / cytology*
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Gonadal Steroid Hormones; 0/Growth Substances; 0/Proliferating Cell Nuclear Antigen; 0/Proto-Oncogene Proteins c-bcl-2
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