Biomedical subjects

Hae Hyun Jung

Publications and source records attributed to Hae Hyun Jung.

5 recordsLinked to original sources

PubMed2006

Platelet-activating factor-induced NF-kappaB activation enhances VEGF expression through a decrease in p53 activity.

We investigated the role of p53 in nuclear factor (NF)-kappaB dependent, platelet-activating factor (PAF)-induced vascular endothelial growth factor (VEGF) expression. Transfected NF-kappaB subunits in ECV304 cells increased the tumor necrosis factor-alpha promoter activity, which was completely inhibited by p53. Transfected p53 increased p53RE promoter activity, which was completely inhibited by NF-kappaB subunits, indicating that cross-regulation occurs between NF-kappaB and p53. PAF-induced increase in VEGF expression was correlated with decreased p53 activity. These data suggest that NF-kappaB-dependency of the PAF-induced increase in VEGF expression is due to decreased p53 activity, which is reciprocally regulated by increased NF-kappaB activity.

Cells, Cultured↗

PubMed2006

Interferon-alpha resistance can be reversed by inhibition of IFN-alpha-induced COX-2 expression potentially via STAT1 activation in A549 cells.

The current study demonstrates that COX-2 expression is positively regulated by IFN-alpha, which is mediated by activation of STAT1 in A549 cells. The IFN-alpha-induced COX-2 expression and STAT1 activation were markedly inhibited by the addition of curcumin to the IFN-alpha-pretreated cells. While IFN-alpha or COX-2 inhibitors alone did not result in growth inhibition of A549 cells, the combination of IFN-alpha and celecoxib or curcumin resulted in a significant growth inhibition of A549 cells, which was associated with down-regulation of CDK2, 4, and 6 and up-regulation of p27. We demonstrate that the expression of COX-2 was induced by IFN-alpha possibly via STAT1 activation in the A549 human non-small cell lung cancer cell line, which may partly account for its IFN-alpha resistance. The addition of curcumin or celecoxib to the IFN-alpha-pretreated A549 cells altered the IFN-alpha sensitivity of cell growth inhibition.

Carcinoma, Non-Small-Cell Lung↗

PubMed2005

Curcumin inhibits interferon-alpha induced NF-kappaB and COX-2 in human A549 non-small cell lung cancer cells.

The A549 cells, non-small cell lung cancer cell line from human, were resistant to interferon (IFN)-alpha treatment. The IFN-alpha-treated A549 cells showed increase in protein expression levels of NF-kappaB and COX-2. IFN-alpha induced NF-kappaB binding activity within 30 min and this increased binding activity was markedly suppressed with inclusion of curcumin. Curcumin also inhibited IFN-alpha-induced COX-2 expression in A549 cells. Within 10 min, IFN-alpha rapidly induced the binding activity of a gamma-(32)P-labeled consensus GAS oligonucleotide probe, which was profoundly reversed by curcumin. Taken together, IFN-alpha-induced activations of NF-kappaB and COX-2 were inhibited by the addition of curcumin in A549 cells.

Carcinoma, Non-Small-Cell Lung↗

PubMed2005

STAT1 and Nmi are downstream targets of Ets-1 transcription factor in MCF-7 human breast cancer cell.

Ets-1 is a cellular homologue of the product of the viral ets oncogene of the E26 virus, and it functions as a tissue-specific transcription factor. It plays an important role in cell proliferation, differentiation, lymphoid cell development, transformation, angiogenesis, and apoptosis. Ets-1 controls the expression of critical genes involved in these processes by binding to ets binding sites present in the transcriptional regulatory regions. Here, we transiently overexpressed Ets-1 in MCF-7 and comprehensively searched for potential downstream targets of Ets-1 by cDNA microarray analysis. The expressions of several interferon-related genes including STAT1 and Nmi were augmented by the overexpression of Ets-1. RT-PCR and Western blotting confirmed the increase in the levels of STAT1 and Nmi mRNA and protein. In contrast, Ets-1 siRNA decreased the expression of STAT1 and Nmi proteins. As in our transient transfection experiments, stable overexpression of Ets-1, also increased the protein expression of STAT1 and Nmi in MCF-7 cells. Taken together, our results indicate that STAT1 and Nmi are downstream targets of Ets-1 in MCF-7 human breast cancer cells.

Actins↗

PubMed2004

Essential role for platelet-activating factor-induced NF-kappaB activation in macrophage-derived angiogenesis.

Activated monocyte-macrophages have been implicated in tumor angiogenesis via their capacity to produce many potent angiogenic factors. However, the mechanisms leading to production of these angiogenic factors in macrophages remain to be elucidated. In this study, we demonstrated by use of a mouse Matrigel implantation model that mouse peritoneal macrophages induce angiogenesis. mRNA expression and protein synthesis of macrophage-derived crucial angiogenic factors such as IL-1, TNF-alpha, basic fibroblast growth factor, and vascular endothelial growth factor (VEGF) were blocked by platelet-activating factor (PAF) receptor antagonists. It was also observed that inhibitors of NF-kappaB blocked macrophage production of these angiogenic factors. Gene expression and protein synthesis of the angiogenic factors cited above were also inhibited in IkappaBalpha-mutated macrophages. VEGF is the most potent angiogenic factor in macrophage-induced angiogenesis. PAF antagonists or NF-kappaB inhibitors also inhibit the capacity of conditioned medium from LPS-stimulated human peripheral blood monocytes to induce sprouting of porcine pulmonary arterial endothelial cells. These data indicate that PAF-induced NF-kappaB activation is a common upstream pathway leading to the production of crucial macrophage-derived angiogenic factors. This will provide an important clue for a better understanding of mechanisms involved in tumor angiogenesis.

Angiogenesis Inducing Agents↗