Document Detail


GDF-9 promotes the growth of prostate cancer cells by protecting them from apoptosis.
MedLine Citation:
PMID:  20458753     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bone morphogenetic proteins (BMPs) have long been implicated in the process of prostate cancer progression and bone metastasis. This current study investigates the role of GDF-9, a BMP member, in prostate cancer. GDF-9 was over-expressed in PC-3 cells using a mammalian expression construct. Additionally, GDF-9 ribozyme transgenes were generated in order to knock down the expression of GDF-9 in PC-3 and DU-145 cells. These cells were then used in in vitro growth assays in order to determine the effect of GDF-9 on prostate cancer cell growth. Recombinant GDF-9 was also generated and used to treat both cell lines before carrying out further growth assays. Levels of apoptosis were subsequently analyzed using flow cytometry. Cell growth was significantly increased in the GDF-9 over-expressing cells compared to the two controls. The cell growth rate at day 5 was significantly greater in the PC-3(GDF-9exp.) (1,131.1 +/- 79.1%) compared to both PC-3(WT) (563.9 +/- 90.6%) and PC-3(pEF) (763.3 +/- 82.0%), P <or= 0.001 versus both controls. The opposite effect was seen in both PC-3 and DU-145 GDF-9 knockdown cells. The PC-3(WT) cells treated with rh-GDF-9 (1.35 +/- 0.28) had a significantly increased absorbance and hence growth rate compared to the untreated PC-3 cells (0.79 +/- 0.05), P = 0.026. Finally, flow cytometry and Hoechst 33342 DNA staining demonstrated decreased apoptosis and caspase-3 expression levels in PC-3(GDF-9exp.) cells and rh-GDF-9-treated PC-3(WT) cells. This study shows that GDF-9 can promote the growth rate of both PC-3 and DU-145 cells by protecting the cells from caspase-3-mediated apoptosis, and suggests that GDF-9 may aid in the progression of prostate cancer by acting as a survival factor.
Authors:
Sivan M Bokobza; Lin Ye; Howard G Kynaston; Wen G Jiang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  225     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-08-30     Completed Date:  2010-10-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  529-36     Citation Subset:  IM    
Copyright Information:
(c) 2010 Wiley-Liss, Inc.
Affiliation:
Metastasis & Angiogenesis Research Group, Department of Surgery, Cardiff University School of Medicine, Cardiff, UK. bokobzasm@cf.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / physiology*
Biological Markers
Cell Line, Tumor
Cell Proliferation
Gene Expression Regulation, Neoplastic / physiology*
Growth Differentiation Factor 9 / genetics,  metabolism*,  pharmacology
Humans
Male
Prostatic Neoplasms / etiology,  metabolism,  pathology*
Recombinant Proteins / pharmacology
Time Factors
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Growth Differentiation Factor 9; 0/Recombinant Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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