Document Detail


Pamidronate down-regulates urokinase-type plasminogen activator expression in PC-3 prostate cancer cells.
MedLine Citation:
PMID:  18225541     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Bisphosphonates are considered to be effective in preventing tumor metastasis to bone. Urokinase-type plasminogen activator (uPA) is thought to be critically involved in the metastatic phenotype of prostate cancer. In this study, we examined the effect of pamidronate on uPA expression in PC-3 prostate cancer cells. MATERIALS AND: The mRNA expression of uPA was assayed by real-time RT-PCR. The transcriptional activity of uPA was measured by a luciferase assay. RESULTS: Pamidronate inhibited uPA mRNA expression by about 90% at 24 h. The inhibition of uPA mRNA expression was prevented in part by cotreatment with geranylgeranyl diphosphate (GGPP). Moreover, GGTI-286, a selective inhibitor of geranylgeranyl transferase, also inhibited uPA mRNA expression. The luciferase activity of uPA reporter plasmid was significantly inhibited by pamidronate. CONCLUSION: These results indicate that the decrease in uPA expression brought about by pamidronate is dependent on the inhibition of geranylgeranylation of proteins and occurs at the transcriptional level.
Authors:
Kazuhiro Iguchi; Yoshiki Tatsuda; Shigeyuki Usui; Kazuyuki Hirano
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  27     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2007 Nov-Dec
Date Detail:
Created Date:  2008-01-29     Completed Date:  2008-02-12     Revised Date:  2010-10-19    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  3843-8     Citation Subset:  IM    
Affiliation:
Laboratory of Pharmaceutics, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Diphosphonates / pharmacology*
Diterpenes / pharmacology
Down-Regulation / drug effects
Humans
Male
Polyisoprenyl Phosphates / pharmacology
Prostatic Neoplasms / drug therapy*,  enzymology*,  genetics
RNA, Messenger / biosynthesis,  genetics
Serine Proteinase Inhibitors / pharmacology
Transcription, Genetic / drug effects
Urokinase-Type Plasminogen Activator / antagonists & inhibitors*,  biosynthesis,  genetics
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Diphosphonates; 0/Diterpenes; 0/Polyisoprenyl Phosphates; 0/RNA, Messenger; 0/Serine Proteinase Inhibitors; 40391-99-9/pamidronate; 6699-20-3/geranylgeranyl pyrophosphate; EC 3.4.21.73/Urokinase-Type Plasminogen Activator

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


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