Involvement of MAPK pathway in hypoxia-induced up-regulation of urokinase plasminogen activator receptor in a human prostatic cancer cell line, PC3MLN4
Experimental & Molecular Medicine
; : 57-64, 2004.
Article
in En
| WPRIM
| ID: wpr-190973
Responsible library:
WPRO
ABSTRACT
Clinical studies have shown that tumor hypoxia is associated with invasive growth and metastasis and may be an important prognostic factor adversely influencing survival in patients with tumors. To investigate the mechanisms involved in hypoxia-induced invasive growth and metastasis, hypoxia-mediated urokinase plasmalogen activator receptor (uPAR) expression, cellular invasiveness, and mitogen activated protein kinase (MAPK) activation were measured in a prostate cancer cell line, PC3MLN4. The levels of uPAR expression and cellular invasiveness were increased in hypoxic cells. Hypoxia-induced cellular invasiveness was blocked by an anti-uPAR monoclonal antibody. Phosphorylations of ERK and p38 kinases were also more extensive in hypoxic cells than in normoxic cells. Hypoxia-induced uPAR up-regulation was inhibited by pre-treatments with a specific inhibitor of MEK, PD98059 and a specific inhibitor of p38 MAP kinase, SB203580. Cell growth also increased in hypoxic cells. From these results, hypoxia increased tumor cell invasion by up-regulating uPAR expression, which might be mediated through ERK and p38 kinase signaling pathways in PC3MLN4 prostate cancer cell line.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Phosphorylation
/
Prostatic Neoplasms
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Up-Regulation
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Receptors, Cell Surface
/
Mitogen-Activated Protein Kinases
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MAP Kinase Signaling System
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Cell Line, Tumor
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Protein Kinase Inhibitors
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Cell Proliferation
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Hypoxia
Type of study:
Prognostic_studies
Limits:
Animals
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Humans
/
Male
Language:
En
Journal:
Experimental & Molecular Medicine
Year:
2004
Type:
Article