• Molecules and Cells
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• v.26 no.5
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• pp.462-467
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• 2008

TPA is known to cooperate with an activated Ras oncogene in the transformation of rodent fibroblasts, but the biochemical mechanisms responsible for this effect have not been established. In the present study we used c-fos promoter-luciferase constructs as reporters, in transient transfection assays, in NIH3T3 cells to assess the mechanism of this cooperation. We found a marked synergistic interaction between TPA and a transfected v-Ha-ras oncogene in the activation of c-fos promoter and SRE. SRE has binding sites for TCF and SRF. A dominant-negative Ras (ras-N17) inhibited the TPA-Ras synergy by blocking the PKC-MAPK-TCF pathway. Dominant-negative RhoA and Rac1 (but not Cdc42Hs) inhibited the TPA-Ras synergy by blocking the Ras-Rho-SRF signaling pathway. Constitutively active $PKC{\alpha}$ and $PKC{\varepsilon}$ showed synergy with v-Ras. These results suggest that the activation of two distinct pathways such as Ras-Raf-ERK-TCF pathway and Rho-SRF pathway are responsible for the induction of c-fos by TPA and Ras in mitogenic signaling pathways.

• ALGAE
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• v.35 no.4
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• pp.325-335
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• 2020

A new diatom species, Mayamaea vietnamica sp. nov., is described from Cát Tiên National Park in Vietnam. This species was discovered and described from soil samples. Algae from soil ecosystems in Vietnam are almost unknown. The new species is described on the basis of an integrated approach with molecular and morphological data, and comparison with similar species. In terms of molecular data, 18S rDNA (including V4 domain), and partial rbcL plastid genes show M. vietnamica sp. nov. is most closely related to M. terrestris N. Abarca and R. Jahn, and together they form a monophyletic group relative to other members of the genus. M. vietnamica sp. nov. differs from other species in the genus by the number of striae and areolae in 10 ㎛, number of areolae per stria, as well as shape and presence or absence of axial and central areas.

• Nuclear industry
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• v.18 no.7 s.185
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• pp.64-69
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• 1998

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.107-107
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• 2001

During the last decade, enormous progress has been made on the biological significance of apoptosis. Since ras is among the most central molecule in signaling, we asked if ras regulates apoptotic pathway. We have previously shown that H-ras, but not N-ras, induces an invasiveness and motility in human breast epithelial cells (MCF10A), while both H-ras and N-ras induce transformed phenotype. In this study, we wished to seek a chemopreventive agent that effectively induces apoptosis in H-ras-activated cells. Here we show that capsaicin, the major pungent phytochemical in red pepper, induces caspase 3-involved apoptosis selectively in H-ras activated MCF10A cells while the parental MCF10A cells are not effected. In order to study the molecular mechanisms for the increased sensitivity of H-ras MCF10A cells to capsaicin-induced apoptosis, activation of ras downstream signaling molecules, mitogen-activated protein kinases (MAPKinases), upon capsaicin treatment was investigated. Phosphorylated forms of JNK1 and p38 MAPKinase were prominently increased whereas activated ERK-1/2 was decreased by capsaicin in ras-activated cells. The parental cells did not respond to capsaicin, suggesting that capsaicin selectively induces apoptosis through modulating activities of ras downstream signaling molecules in H-ras-activated cells. Studies using chemical inhibitors (CPT-cAMP, SB203580 and PD98059) and dominant negative constructs of JNKl, p38 and MEK show that activation of JNK1 and p38 MAPKinase, but not ERK-1/2, is critical for ras-mediated apoptosis by capsaicin.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.157-157
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• 2001

One of the most frequent defects in human cancer is the uncontrolled activation of the ras-signaling pathways. We have previously shown that H-ras, but not N-ras, induces an invasiveness and motility in human breast epithelial cells (MCF10A), while both H-ras and N-ras induce transformed phenotype. Since migration plays a crucial role in invasive, we examined motility of MCF10A cells transformed with H-ras of N-ras.(omitted)

• BMB Reports
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• v.29 no.5
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• pp.484-487
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• 1996

The matrix metalloproteinases (MMPs) are members of a unique family of proteolytic enzymes that degrade components of the extracellular matrix. Significant evidence has accumulated to directly implicate members of the MMPs in tumor invasion and metastasis formation. To investigate the correlation between ras oncogene and MMP gene expression in various tumor cells, we detected mRNAs for the ras, MMP-2 and MMP-9 (72 kD and 92 kD type IV collagenases, respectively) genes in nine human tumor cell lines. The ras gene was expressed in seven cell lines; MMP-2 in three; MMP-9 in two cell lines tested. There was no direct correlation between the ras oncogene and MMP expression. A clear difference in the mRNA expression between MMP-2 and MMP-9 was observed among the cell lines. As an approach to study the effect of the ras oncogene on metastasis, we examined the expressions of MMP-2 and MMP-9 in HT1080 cells transfected with the v-H-ras gene. MMP-9 expression was Significantly enhanced in the ras-transfected HT1080 cells compared with the nontransfectants while ras transfection did not affect the expression of MMP-2. These results suggest the possible inducing effect of the ras oncogene on the metastasis by activation of the MMP-9 gene in HT1080.

• Proceedings of the Korean Institute of Surface Engineering Conference
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• 2013.05a
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• pp.45-45
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• 2013

• BMB Reports
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• v.49 no.9
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• pp.455-456
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• 2016

Mutations of APC and KRAS are frequently observed in human colorectal cancers (CRCs) and the Wnt/β-catenin and Ras pathways are consequently activated in a significant proportion of CRC patients. Mutations in these two genes are also known to synergistically induce progression of CRCs. Through a series of studies, we have demonstrated that inhibition of the Wnt/β-catenin signaling pathway negatively regulates Ras stability, therefore, Ras abundance is increased together with β-catenin in both mice and human CRCs harboring adenomatous polyposis coli (APC) mutations. In a recent study, we identified KY1220, a small molecule that simultaneously degrades β-catenin and Ras by inhibition of the Wnt/β-catenin pathway, and obtained its derivative KYA1797K, which has improved activity and solubility. We found that KYA1797K binds the RGS domain of axin and enhances the binding affinity of β-catenin or Ras with the β-catenin destruction complex components, leading to simultaneous destabilization of β-catenin and Ras via GSK3β activation. By using both in vitro and in vivo studies, we showed that KYA1797K suppressed the growth of CRCs harboring APC and KRAS mutations through destabilization of β-catenin and Ras. Therefore, our findings indicate that the simultaneous destabilization of β-catenin and Ras via targeting axin may serve as an effective strategy for inhibition of CRCs.

• BMB Reports
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• v.47 no.12
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• pp.685-690
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• 2014

The Ras/Raf/MEK/Erk signaling pathway is important for regulation of cell growth, proliferation, differentiation, survival, and apoptosis in response to a variety of extracellular stimuli. Lack of Erk MAPK activation is observed in several cancer cells despite active activation of Ras. However, little is known about the modulation of Erk1/2 activity by active Ras. Here, we show that overexpression of active H-Ras (H-RasG12R) in NIH3T3 fibroblasts impaired FGF2-induced Erk1/2 phosphorylation, as compared to wild-type cells. Northern blot analysis revealed that prolonged expression of active Ras increased MAP kinase phosphatase 3 (MKP3) mRNA expression, a negative regulator of Erk MAPK. Inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway abrogated active Ras-induced up-regulation of MKP3 expression, leading to the rescue of Erk1/2 phosphorylation. Our results demonstrated that the Ras/Raf/MEK/Erk signaling cascade is negatively regulated by the PI3K/Aktdependent transcriptional activation of the MKP3 gene.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.05a
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• pp.156-156
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• 2001

One of the most frequent defects in human cancer is the uncontroled activation of the ras-signaling pathway. We have previously shown that H-rasm but not N-ras, induces an invasiveness. Here, we show that cell motility was greatly increased by H-ras, but not by N-ras, suggesting that H-ras-induced invasive phnotype involves enhanced cell motility.(omitted)