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- W4233027142 abstract "9684 Background: Hypoxia has been known to be involved in many pathological processes including tumor formation, where it has been associated with resistance to treatment and malignant progression. 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. Methods: To investigate the mechanisms involved in hypoxia-induced invasive growth and metastasis, hypoxia-mediated uPAR expression, cellular invasiveness, and mitogen activated protein kinase (MAPK) activation were measured in a prostate cancer cell line, PC3MLN4. In order to investigate whether exposure to hypoxia increases the expression of uPAR in PC3MLN4 cells, the cells were incubated under either hypoxia or normoxia for 24 hrs and then the level of uPAR was measured using a flow-cytometry. Results: Hypoxia induced a 2.7 fold increase in the level of cell surface uPAR expression compared to normoxia. And also found hypoxia-induced up-regulation of uPAR mRNA . Hypoxic cells exhibited an invasion rate of 3-fold higher than normoxic cells in standard two-chamber invasion assay. Such a hypoxia-induced cellular invasiveness was blocked by an anti-uPAR monoclonal antibody. Phosphorylations of ERK and p38 kinase were also more extensive in hypoxic cells than in normoxic cells. To test whether ERK and p38 MAP kinase involved in the hypoxia-induced uPAR up-regulation, cells were pretreated with PD 98059 or SB 203580 and the uPAR level was measured by Western blotting. Hypoxia-induced uPAR up-regulation was inhibited by pretreatments with PD 98059 and SB 203580. Cell growth also increased in hypoxic cells. Conclusions: Hypoxia increased tumor cell invasion by up-regulating uPAR expression, which might be mediated through ERK and p38 kinase signaling pathway in the prostate cancer cell line and uPAR may be a good novel therapeutic target. No significant financial relationships to disclose." @default.
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- W4233027142 date "2004-07-15" @default.
- W4233027142 modified "2023-09-26" @default.
- W4233027142 title "Involvement of MAPK pathway in hypoxia-induced up-regulation of urokinase plasminogen activator receptor in a human prostatic cancer cell line, PC3MLN4" @default.
- W4233027142 doi "https://doi.org/10.1200/jco.2004.22.14_suppl.9684" @default.
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