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Prostate. 2004 Jan 1;58(1):95-102.

Activation of the Raf-1/MEK/Erk kinase pathway by a novel Cdc25 inhibitor in human prostate cancer cells.

Author information

1
Department of Urology, Nippon Medical School, Tokyo, Japan.

Abstract

BACKGROUND:

The serine/threonine kinase Raf-1 is a major regulator of the mitogen activated protein kinase (MAPK) pathway, which has been associated with the progression of prostate cancer to the more advanced and androgen-independent disease. Cdc25A phosphatase has been implicated in the regulation of Raf-1 and the MAPK pathway.

METHODS:

We used a novel and potent Cdc25A inhibitor, 2,3-bis-[2-hydroxyethylsulfonyl]-[1,4] naphthoquinone (NSC 95397), and its congener (2-mercaptoethanol)-3-methyl-1, 4-naphthoquinone (NSC 672121) to study the role of Cdc25A on the MAPK pathway in human prostate cancer cells.

RESULTS:

We found Raf-1 physically interacted with Cdc25A in PC-3 and LNCap cells and inhibitors of Cdc25A induced both extracellular signal-regulated kinase (Erk) activation and Raf-1 tyrosine phosphorylation. NSC 95397 attenuated Cdc25A and Raf-1 interactions due to accelerated degradation of Cdc25A, which was mediated by proteasome degradation. The MAPK kinase (MEK) inhibitor U0126 completely inhibited Erk activation by NSC 95397 and NSC 672121.

CONCLUSIONS:

These results indicate Cdc25A phosphatase regulates Raf-1/MEK/Erk kinase activation in human prostate cancer cells.

PMID:
14673957
DOI:
10.1002/pros.10292
[Indexed for MEDLINE]

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