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Urokinase plasminogen activator receptor (uPAR) expression is reduced by tyrosine kinase inhibitors
Author(s) -
SKOGSETH HAAKON,
LARSSON ERIK,
HALGUNSET JOSTEIN
Publication year - 2006
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/j.1600-0463.2006.apm_248.x
Subject(s) - urokinase receptor , tyrosine kinase , microbiology and biotechnology , immunocytochemistry , receptor tyrosine kinase , cancer research , chemistry , receptor , biology , plasminogen activator , endocrinology , biochemistry
Previously we reported that tyrosine kinase inhibitors (TKI) produced a reduction in uPA expression in prostatic cancer cells, and that TKI‐treated cells were less invasive compared to untreated cells. Nevertheless, no change in cell migration was observed when TKI‐treated cells were supplied with external uPA, thus indicating more complex mechanisms leading to decreased cell invasion. uPAR expression was measured with an enzyme‐ linked immunosorbent assay (ELISA) in PC‐3 and DU‐145 prostate carcinoma cells treated with the two TKI genistein and AG‐1478. uPAR mRNA levels were measured with real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR). uPAR immunocytochemistry was used to examine the receptor distribution in cells grown on a reconstituted basal lamina. Immunocytochemistry showed an intense uPAR immunostaining in invading cells, particularly in the leading edge membrane. Treatment with genistein and AG‐1478 led to a decreased expression of uPAR in DU‐145, but not in PC‐3. Furthermore, a reduction of uPAR mRNA was found in TKI‐treated DU‐145 cells, while PC‐3 was not affected. Our results indicate a possible role of TKI as cancer suppressors by acting as a regulator of uPAR expression.