• 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.

• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.21 no.3
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• pp.314-318
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• 1992

The sarcoma 180 cells were treated with ursolic acid which was previously extracted from leaves of Eriobotrya japonica Lindy (Rosaceae) and identified as a potent anticarinogenic agent. Suppressing effects of the compounds with testing changes in selected oncogenes expression were examined by using the northern hybridization method. Ursolic acid significantly suppressed c-myc oncogene expression. However, c-ha-ras oncogene expression was lowered slightly with the ursolic acid treatment. Therefore, it was concluded that preproven anticarcinogenic effects of ursolic acid should be partly ascribed to the modified oncogenic expression.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.759-769
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• 2002

Mutated forms of ras are found in many human tumors and the rate of incidence is significantly higher in colon and pancreatic cancers. The protein product from the ras oncogene is a small G-protein, $p21^{ras}{\;}(Ras)$ that is known to playa key role in the signal transduction cascade and cell differentiation and proliferation. Mutated Ras is unable to regulate itself and remains constantly activated, leading to uncontrolled cell growth. The function of Ras in signal transduction requires its location near the growth factor receptor at the cell membrane. However, Ras does not have a transmembrane domain. Ras requires farnesylation to increase its hydrophobicity and subsequent plasma membrane association for its transforming activity. This key post-translational modification is catalyzed by the enzyme Ras farnesyltransferase (FTase), which transfers a farnesyl group from farnesylpyrophosphate to the C-terminal cysteine of the Ras protein. The requirement has focused attention on FTase as a target for therapeutic intervention. Selective inhibition of FTase will prevent Ras protein from association with the plasma membrane, leading to a disruption of oncogenic Ras function.

• Journal of Animal Reproduction and Biotechnology
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• v.35 no.1
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• pp.12-20
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• 2020

Cell adhesion plays an important role in the differentiation of the morphogenesis and the trophectoderm epithelium of the blastocyst. In the porcine embryo, CDH1 mediated adhesion initiates at compaction before blastocyst formation, regulated post-translationally via protein kinase C and other signaling molecules. Here we focus on muscle RAS oncogene homolog (M-RAS), which is the closest relative to the RAS related proteins and shares most regulatory and effector interactions. To characterize the effects of M-RAS on embryo compaction, we used gain- and loss-of-function strategies in porcine embryos, in which M-RAS gene structure and protein sequence are conserved. We showed that knockdown of M-RAS in zygotes reduced embryo development abilities and CDH1 expression. Moreover, the phosphorylation of ERK was also decreased in M-RAS KD embryos. Overexpression of M-RAS allows M-RAS KD embryos to rescue the embryo compaction and blastocyst formation. Collectively, these results highlight novel conserved and multiple effects of M-RAS during porcine embryo development.

• Asian-Australasian Journal of Animal Sciences
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• v.7 no.1
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• pp.119-124
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• 1994

Experiments were performed to determine age-associated changes in ornithine decarboxylase (ODC) gene and Ha-ras cellular oncogene expression in tissues of female rats. In the kidney, ODC mRNA levels did not show age-associated changes, while ODC enzyme activities were decreased with advancing age from 3 to 10 months. These results suggest that post-transcriptional mechanism (s) are involved in the age-dependent decrease in renal ODC enzyme activity. In addition, we found no correlation between testosterone-induced renal ODC expression and DNA methylation pattern. Ha-ras mRNA levels in brain decreased as animals aged from 3 to 6 months, while renal Ha-ras mRNA levels were not influenced by age. Results demonstrate the age-dependent expression of Ha-ras in a tissue-specific manner.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2699-2701
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• 2013

The RAS family genes encode small GTP-binding cytoplasmic proteins. Activated KRAS engages multiple effector pathways, notably the RAF-mitogen-activated protein kinase, phosphoinositide-3-kinase (PI3K) and RalGDS pathways. In the clinical field, K-ras oncogene activation is frequently found in human cancers and thus may serve as a potential diagnostic marker for cancer cells in circulation. This mini-review aims to summarise information on Ras-induced oncogenesis and the clinical significance of K-ras.

• Molecules and Cells
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• v.43 no.10
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• pp.889-897
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• 2020

K-RAS is frequently mutated in human lung adenocarcinomas (ADCs), and the p53 pathway plays a central role in cellular defense against oncogenic K-RAS mutation. However, in mouse lung cancer models, oncogenic K-Ras mutation alone can induce ADCs without p53 mutation, and loss of p53 does not have a significant impact on early K-Ras-induced lung tumorigenesis. These results raise the question of how K-Ras-activated cells evade oncogene surveillance mechanisms and develop into lung ADCs. RUNX3 plays a key role at the restriction (R)-point, which governs multiple tumor suppressor pathways including the p14^ARF-p53 pathway. In this study, we found that K-Ras activation in a very limited number of cells, alone or in combination with p53 inactivation, failed to induce any pathologic lesions for up to 1 year. By contrast, when Runx3 was inactivated and K-Ras was activated by the same targeting method, lung ADCs and other tumors were rapidly induced. In a urethane-induced mouse lung tumor model that recapitulates the features of K-RAS-driven human lung tumors, Runx3 was inactivated in both adenomas (ADs) and ADCs, whereas K-Ras was activated only in ADCs. Together, these results demonstrate that the R-point-associated oncogene surveillance mechanism is abrogated by Runx3 inactivation in AD cells and these cells cannot defend against K-Ras activation, resulting in the transition from AD to ADC. Therefore, K-Ras-activated lung epithelial cells do not evade oncogene surveillance mechanisms; instead, they are selected if they occur in AD cells in which Runx3 has been inactivated.

• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2001.09a
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• pp.13-15
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• 2001

발암성시험연구에 사용되고 있는 형질전환 동물들은 랫드와 마우스 등이 있는데, 그 중 c-Ha-ras proto-oncogene 마우스 (ras H2 mice), v-Ha-ras 형질전환 마우스 (Tg.AC mice), pim-1 형질전환 마우스 및 p53 knockout 마우스 등이 발암유발물질에 감수성이 높아 현재 중기발암성시험에 이용되고 있다. (중략)

• Journal of the Korean Society of Food Science and Nutrition
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• v.25 no.6
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• pp.1024-1030
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• 1996

Capsaicin (8-methyl-N-vanillyl-6-nonenamide: CAP) is a mai or ingredient of hot pepper that has been used as a spicy food additive, preservative, and medicine. In this study, we evaluated the effect of dietary CAP on the selected proto-oncogene(c-jun, c-myc, H-ras, erbB, p53) expressions in various tissues of mice. Male ICR mice were divided into four groups and fed the experimental diets containing CAP at the levels of 0, 5, 20 and 100ppm for four weeks. Steady state RNA levels in various tissues were measured by slot blot hybridization assay. C-jun expression level was enhanced in stomach tissue from mice fed 20ppm CAP and significantly reduced from mice fed 100ppm CAP. The c-jun expression levels were differentially altered in organ-specific manner, Tumor suppressor gene p53 expression level appeared to be slightly increased in the liver from mice fed 20ppm CAP. These results suggested that dietary CAP differentially modulates c-jun and p53 expression in various organs.