Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.10 (IKK)
 4,900 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the most frequent events in carcinogenesis is uncontrolled activation of Ras signaling pathway. A previous study demonstrated that the introduction of H-Ras into the normal WB-F344 rat liver epithelial (WB) cell line and adult male F344 rats resulted in tumorigenicity. The present study investigated whether H-Ras induced the invasive and migrative phenotypes in WB cells, and subsequently aimed at characterizing the underlying mechanisms. H-Ras induced the invasive and migrative phenotypes of WB cells with a selective up-regulation of matrix metalloproteinase (MMP)-9, but not MMP-2. Cyclooxygenase (COX)-2 and the subsequent production of prostaglandin E2 (PGE2) were also induced by H-Ras. Treatment of H-Ras WB cells with GM6001 and NS398, the inhibitors of MMPs and COX-2, respectively, significantly inhibited the H-Ras-induced invasive and migrative phenotypes. DNA binding activity of nuclear factor (NF)-kappaB, but not that of activator protein (AP)-1, was increased by H-Ras. Caffeic acid phenethyl ester and Bay 11-7082, specific inhibitors of NF-kappaB and IKK, respectively, significantly inhibited the expression of MMP-9 and COX-2, invasion and migration of H-Ras WB cells, revealing NF-kappaB as a transcriptional factor responsible for H-Ras-induced malignant phenotypic conversion of WB cells. Activation of ERKs pathway was critical for H-Ras-induced invasive and migrative phenotypes, up-regulation of MMP-9 and COX-2 as well as enhanced DNA binding activity of NF-kappaB in WB cells. Taken together, these results demonstrate that H-Ras up-regulates MMP-9 and COX-2 through activation of ERKs and IKK-IkappaBalpha-NF-kappaB signal pathway which may contribute to the malignant progression of WB rat liver epithelial cells.
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PMID:H-Ras selectively up-regulates MMP-9 and COX-2 through activation of ERK1/2 and NF-kappaB: an implication for invasive phenotype in rat liver epithelial cells. 1672 10

Caffeic acid phenethyl ester (CAPE), an active component of propolis extracts, has been known for its specific inhibition of nuclear factor kappaB (NF-kappaB) and subsequent anti-inflammatory activity. In this study, we report that (i) CAPE exerts its anti-inflammatory action (inhibition of tumor necrosis factor-induced expression of intercellular adhesion molecule-1 and CC chemokine ligand-2) via NF-kappaB inhibition by two distinct molecular mechanisms in a cell-specific manner: CAPE inhibited downstream pathways of inhibitor kappaB (IkappaB) degradation in monocytic cells, while activation of upstream IkappaB kinase was suppressed by CAPE pre-treatment in astroglial cells; and (ii) CAPE paradoxically activates the c-Jun N-terminal kinase (JNK) pathway, which might be responsible for its pro-apoptotic action and divergent regulation of proinflammatory mediators such as CXC chemokine ligand-8.
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PMID:Differential regulation of c-Jun N-terminal kinase and NF-kappaB pathway by caffeic acid phenethyl ester in astroglial and monocytic cells. 1808 68