• International Journal of Stem Cells
• /
• v.16 no.2
• /
• pp.215-233
• /
• 2023

Background and Objectives: MYC, also known as an oncogenic reprogramming factor, is a multifunctional transcription factor that maintains induced pluripotent stem cells (iPSCs). Although MYC is frequently upregulated in various cancers and is correlated with a poor prognosis, MYC is downregulated and correlated with a good prognosis in lung adenocarcinoma. MYC and two other MYC family genes, MYCN and MYCL, have similar structures and could contribute to tumorigenic conversion both in vitro and in vivo. Methods and Results: We systematically investigated whether MYC family genes act as prognostic factors in various human cancers. We first evaluated alterations in the expression of MYC family genes in various cancers using the Oncomine and The Cancer Genome Atlas (TCGA) database and their mutation and copy number alterations using the TCGA database with cBioPortal. Then, we investigated the association between the expression of MYC family genes and the prognosis of cancer patients using various prognosis databases. Multivariate analysis also confirmed that co-expression of MYC/MYCL/MYCN was significantly associated with the prognosis of lung, gastric, liver, and breast cancers. Conclusions: Taken together, our results demonstrate that the MYC family can function not only as an oncogene but also as a tumor suppressor gene in various cancers, which could be used to develop a novel approach to cancer treatment.

• Journal of Life Science
• /
• v.29 no.1
• /
• pp.9-17
• /
• 2019

As tumors develop, they encounter microenvironmental stress, such as hypoxia and glucose depletion, due to poor vascular function, thereby leading to necrosis, which is observed in solid tumors. Necrotic cells are known to release cellular cytoplasmic contents, such as high mobility group box 1 (HMGB1), into the extracellular space. The release of HMGB1, a proinflammatory and tumor-promoting cytokine, plays an important role in promoting inflammation and metabolism during tumor development. Recently, HMGB1 was shown to induce the epithelial-mesenchymal transition (EMT) and metastasis. However, the underlying mechanism of the HMGB1-induced EMT, invasion, and metastasis is unclear. In this study, we showed that noninvasive breast cancer cells MCF-7 formed tightly packed, rounded spheroids and that the cells in the inner regions of a multicellular tumor spheroid (MTS), an in vitro model of a solid tumor, led to necrosis due to an insufficient supply of O2 and glucose. In addition, after 7 d of MTS culture, the EMT was induced via the transcription factor Snail. We also showed that HMGB1 receptors, including RAGE, TLR2, and TLR4, were induced by MTS culture. RAGE, TLR2, and TLR4 shRNA inhibited MTS growth, supporting the idea that RAGE/TLR2/TLR4 play critical roles in MTS growth. They also prevented MTS culture-induced Snail expression, pointing to RAGE/TLR2/TLR4-dependent Snail expression. RAGE, TLR2, and TLR4 shRNA suppressed the MTS-induced EMT. In human cancer tissues, high levels of RAGE, TLR2, and TLR4 were detected. These findings demonstrated that the HMGB-RAGE/TLR2/TLR4-Snail axis played a crucial role in the growth of the MTS and MTS culture-induced EMT.

• Analytical Science and Technology
• /
• v.24 no.6
• /
• pp.510-518
• /
• 2011

Recent developments and improvements of multiple technological elements including mass spectrometry (MS) instrument, multi-dimensional chromatographic separation, and software tools processing MS data resulted in benefits of large scale proteomics analysis. However, its throughput is limited by the speed and reproducibility of the protein digestion process. In this study, we demonstrated a new method for rapid proteolytic digestion of proteins using acoustic technology. Tryptic digests of BSA prepared at various conditions by super acoustic for optimization time and intensity were analyzed by LC-MS/MS showed higher sequence coverage in compared with traditional 16 hrs digestion method. The method was applied successfully for complex proteins of a breast cancer cells at 30 min of digestion at intensity 2. This new application reduces time-consuming of sample preparation with better efficiency, even with large amount of proteins, and increases high-throughput process in sample preparation state.

• Journal of Microbiology and Biotechnology
• /
• v.10 no.3
• /
• pp.293-299
• /
• 2000

Many methods have been developed for screening chemicals with hormonal activity. Using recombinant yeasts expressing either human estrogen receptor [Saccharomyces cerevisiae ER + LYS 8127 (YER)] or androgen receptor [S. cerevisiae AR + 8320 (YAR)], we evaluated the hormonal activities of several chemicals by induction of ${\beta}-galactosidase$ activity. The chemicals were $17{\beta}-estradiol$ (E2), testosterone (T), ${\rho}-nonylphenol$ (NP), bisphenol A (BPA), genistein (GEN), 2-bromopropane (2-BP), dibutyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and butylparaben (BP). To assess the estrogenicity of NP, the result of the in vitro recombinant yeast assay was compared with an E-screen assay using MCF-7 human breast cancer cells and an uterotrophid assay using ovariectomized mice. In the YER yeast cells, E2, NP, BPA, GEN, and BP exhibited estrogenicity in a doseresponse manner, while TCDD did not. All the chemicals tested, except T, did not show androgenicity in the YAR yeast cell. The sensitivity of the yeast (YER) assay system to the estrogenic effect of NP was similar to that of the E-screen assay. NP was also estrogenic in the uterotrophic assay. However, in terms of convenience and costs, the yeast assay was superior to the E-screen assay or uterotrophic assay. These results suggest that the recombinant yeast assay can be used as a rapid tool for detecting chemicals with hormonal activities.

• Archives of Pharmacal Research
• /
• v.27 no.9
• /
• pp.906-911
• /
• 2004

In order to evaluate estrogenic compounds in natural products, an in vitro detection system was established. For this system, the human breast cancer cell line MCF7 was stably trans-fected using an estrogen responsive chloramphenicol acetyltransferase (CAT) reporter plas-mid yielding MCF7/pDsCAT-ERE119-Ad2MLP cells. To test the estrogenic responsiveness of this in vitro assay system, MCF7/pDsCAT-ERE119-Ad2MLP cells were treated with various concentrations of 17f3-estradiol. Treatments of 10$^{-8}$ to 10$^{-12}$ M 17$\beta$-estradiol revealed significant concentration dependent estrogenic activities compared with ethanol. We used in vitro assay system to detect estrogenic effects in Puerariae radix and Ginseng radix Rubra extracts. Treat-ment of 500 and 50 $\mu\textrm{g}$/ml of Puerariae radix extracts increased the transcriptional activity approximately 4- and 1.5-fold, respectively, compared with the ethanol treatment. Treatment of 500, 50, and 5 $\mu\textrm{g}$/ml of Ginseng radix Rubra extracts increased the transcriptional activity approximately 3.2-,2.7, and 1.4-fold, respectively, compared with the ethanol treatment. These observations suggest that Puerariae radix and Ginseng radix Rubra extracts have effective estrogenic actions and that they could be developed as estrogenic supplements.

• Molecules and Cells
• /
• v.27 no.3
• /
• pp.351-357
• /
• 2009

Phytoestrogens are the natural compounds isolated from plants, which are structurally similar to animal estrogen, $17{\beta}$-estradiol. Tectoridin, a major isoflavone isolated from the rhizome of Belamcanda chinensis. Tectoridin is known as a phytoestrogen, however, the molecular mechanisms underlying its estrogenic effect are remained unclear. In this study we investigated the estrogenic signaling triggered by tectoridin as compared to a famous phytoestrogen, genistein in MCF-7 human breast cancer cells. Tectoridin scarcely binds to ER ${\alpha}$ as compared to $17{\beta}$-estradiol and genistein. Despite poor binding to ER ${\alpha}$, tectoridin induced potent estrogenic effects, namely recovery of the population of cells in the S-phase after serum starvation, transactivation of the estrogen response element, and induction of MCF-7 cell proliferation. The tectoridin-induced estrogenic effect was severely abrogated by treatment with U0126, a specific MEK1/2 inhibitor. Tectoridin promoted phosphorylation of ERK1/2, but did not affect phosphorylation of ER ${\alpha}$ at $Ser^{118}$. It also increased cellular accumulation of cAMP, a hallmark of GPR30-mediated estrogen signaling. These data imply that tectoridin exerts its estrogenic effect mainly via the GPR30 and ERK-mediated rapid nongenomic estrogen signaling pathway. This property of tectoridin sets it aside from genistein where it exerts the estrogenic effects via both an ER-dependent genomic pathway and a GPR30-dependent nongenomic pathway.

• KSBB Journal
• /
• v.27 no.6
• /
• pp.381-386
• /
• 2012

Obesity increases the risk of many adult diseases, such as atherosclerosis, diabetes, hypertension, ischemic heart disease and breast cancer. Inhibition of adipogenesis is an effective way in the anti-obesity management. Because of main components of Saururus chinensis is flavonoid, it has been showed some improvement by its antioxidant effects on the atherosclerosis, heart disease and diabetic hyperlipidemia. But mechanism of anti-obesity effect of S. chinensis is not clear. We investigated the effects of ethanol extracts of S. chinensis on adipogenesis in the 3T3-L1 pre-adipocyte. The 3T3-L1 cell line is commonly used to study adipogenesis in vitro. In this study, ethanol extracts of S. chinensis significantly decrease the lipid accumulation in the 3T3-L1 cells proved by measuring triglyceride contents and Oil red O staining. The proposed mechanism of inhibition of adipogenesis in the 3T3-L1 cells with ethanol extracts of S. chinensis is down-regulation of transcriptional factors and adipocyte-specific genes such CCAAT/enhancer binding protein ${\alpha}$ ($C/EBP{\alpha}$) and Peroxisome proliferator activated receptor ${\gamma}$ ($PPAR{\gamma}$) in concentration dependent pattern. These results suggest that ethanol extracts of S. chinensis inhibits adipognesis in the 3T3-L1 cells and can be used as a safe and efficient natural substance to manage anti-obesity.

• Journal of Life Science
• /
• v.17 no.2 s.82
• /
• pp.179-184
• /
• 2007

PTK6, an intracellular protein tyrosine kinase, is significantly overexpressed in a majority of breast cancers and has a role in promoting the proliferation of the cancer cells, but not of normal cells. Here, we report high-level production of the catalytic unit of PTK6 fused with Drosophila peptidoglycan recognition protein (PGRT)-LB, in the baculovirus system. We first found that the PGRP-LB was potentially useful as a fusion partner to increase the yield of heterologous protein in the baculovirus system. The purified recombinant protein exhibited a 1.5-fold activity with much higher yield than the bacterially-expressed protein. The protein expressed in the baculovirus system will be useful for the crystallization to determine its crystal structure helping understand the molecular mechanism of PTK6 and design its inhibitors.

• Environmental Mutagens and Carcinogens
• /
• v.24 no.4
• /
• pp.180-188
• /
• 2004

CYP1A1 is known to be inducible by xenobiotic compouds such as polyciclic aromatic hydrocarbons(PAHs) and 2,3,7,8-tetrachloro-dibenzo-p-dioxin(TCDD). These chemicals have been identified worldwide and can have a significant impact on the human health and well being of human and wildlife. Given these issues, the detection and quantification of these chemicals in biological, environmental and food samples is important. We investigated the effect of dietaty flavonoid, such as CYP1A1 promoter activity, 7-ethoxyresorufin-O-deethylase(EROD) activity and CYP1A1 mRNA expression induced by benzo(k)fluoranthene(B(k)F) in MCF-7 cells. Based on the three criteria of frequency of occurrence in the environment, toxicity and potential exposure to humans, B(k)F is one of the top-listed PAHs. We found that B(k)F significantly up-regulates the level of CYP1A1 promoter activity, EROD and CYP1A1 mRNA. when cells were treated with daidzein inhibited the B(k)-induced CYP1A1 prompter activity and mRNA level at high concentration. But daidzein exhibited stimulatory effects B(k)F-induced CYP1A1 promoter activity and mRNA level at low concentration. Overall, results from these studies demonstrate flavonoids might interfere the action of B(k) with AhR system to stimulate CYP1A1 gene expression.

• Environmental Mutagens and Carcinogens
• /
• v.24 no.4
• /
• pp.189-197
• /
• 2004

We investigated the effect of dietaty flavonoid, such as CYP1A1 promoter activity, 7-ethoxyresorufin-O-deethylase(EROD) activity and CYP1A1 mRNA expression induced by benzo(k)fluoranthene(B(k)F) in MCF-7 cells. Based on the three criteria of frequency of occurrence in the environment, toxicity and potential exposure to humans, B(k)F is one of the top-listed PAHs. We found that B(k)F significantly up-regulates the level of CYP1A1 promoter activity, EROD and CYP1A1 mRNA. When cells were treated with morin alonem, it was not changed that EROD and CYP1A1 mRNA, compared to that of control. However, morin inhibited the B(k)-induced CYP1A1 prompter activity and mRNA level at high concentration. But morin exhibited stimulatory effects B(k)F-induced CYP1A1 promoter activity and mRNA level at low concentration. Overall, results from these studies demonstrate morin might interfere the action of B(k) with AhR system to stimulate CYP1A1 gene expression. CYP1A1 is known to be inducible by xenobiotic compouds such as polyciclic aromatic hydrocarbons(PAHs) and 2,3,7,8-tetrachloro-dibenzo-p-dioxin(TCDD). These chemicals have been identified worldwide and can have a significant impact on the human health and well being of human and wildlife. Given these issues, the detection and quantification of these chemicals in biological, environmental and food samples is important.