Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Up-regulation of extracellular-regulated kinases 1/2 (ERK1/2) has been implicated in tumor progression and metastasis in many types of cancer. We have previously shown that ERK1/2 is necessary for invasiveness of Dunning rat prostatic adenocarcinoma cell lines in which levels of activated ERK1/2 correlate with the metastatic potential. Here, we further examined the biological effects of elevated ERK1/2 in the highly metastatic Dunning cell line, MLL, in which the abilities to invade and metastasize are enhanced relative to its progenitor strain. Inhibition of ERK1/2 activation by the MEK1 inhibitor, PD98059, dose-dependently reduced MLL cell invasiveness and motility with similar IC50 values. On the other hand, the abilities of MLL cells to adhere to the extracellular matrix, phosphorylate myosin regulatory light chain and secrete matrix-degrading enzymes, matrix metalloproteinase (MMP)-2 and urokinase plasminogen activator (uPA) were marginally, if at all, affected by PD98059 treatment. These data indicated that the inhibitory effect of PD98059 on the invasiveness of MLL cells was primarily due to the suppression of cell motility, and the up-regulation of ERK1/2 is, at least in part, responsible for the enhanced cellular motility and invasiveness of the MLL cells.
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PMID:PD98059-inhibited invasion of Dunning rat prostate cancer cells involves suppression of motility but not MMP-2 or uPA secretion. 1668 2

Recent evidence suggests that oxidative stress contributes to the pathogenesis of prostate cancer. The present study focused on the effect of apocynin, an inhibitor of NADPH oxidase, on prostate carcinogenesis using the transgenic rat for adenocarcinoma of prostate (TRAP) model. There were no toxic effects with apocynin treatment. The percentages and numbers of carcinomas in both the ventral and lateral prostate were significantly reduced by apocynin treatment, with dose dependence. Reduction of reactive oxygen species by apocynin was confirmed by immunohistochemistry of 8-OHdG and dihydroethidium staining. Positivity of Ki67 was significantly reduced by apocynin treatment, and downregulation of clusterin expression, as well as inactivation of the MEK-ERK1/2 pathway, was a feature of the apocynin treated groups. In human prostate cancer cell line LNCaP, apocynin also inhibited reactive oxygen species production and blocked cell growth by inducing G0/G1 arrest with downregulation of clusterin and cyclin D1. These data suggest that apocynin possesses chemopreventive potential against prostate cancer.
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PMID:Apocynin, an NADPH oxidase inhibitor, suppresses rat prostate carcinogenesis. 2411 88