• BMB Reports
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• v.49 no.12
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• pp.651-652
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• 2016

EphA2 has been implicated in amplifying ErbB2 tumorigenic signaling. One protein that interacts with EphA2 is the Anks1a PTB adaptor. However, the precise role of Anks1a in EphA2-mediated tumorigenesis is unclear. We demonstrated that Anks1a localizes to the ER upon phosphorylation and that the Ankyrin repeats and PTB of Anks1a bind to EphA2 and Sec23, respectively. Thus, Anks1a facilitates the selective packaging of EphA2 into COPII vesicles. Additionally, Anks1a knockout mice, a phenocopy of EphA2 knockout mice, exhibited markedly reduced ErbB2-induced breast tumorigenesis. Strikingly, ErbB2 did not localize to the cell surface following Anks1a knockdown in primary mammary tumor cells over-expressing ErbB2. Importantly, EphA2 was critical for stabilizing ErbB2 through complex formation, but its interaction with Anks1a also facilitated ErbB2 loading into COPII carriers. These findings suggest a novel role for Anks1a in the molecular pathogenesis of breast tumors and possibly other human diseases.

• Honam Mathematical Journal
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• v.40 no.4
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• pp.809-816
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• 2018

The aim of this research paper is to evaluate fifty double integrals invoving generalized hypergeometric function (25 each) in the form of $${{\int}^1_0}{{\int}^1_0}\;x^{{\gamma}-1}y^{{\gamma}+c-1}(1-x)^{c-1}(1-y)^{c+{\ell}}(1-xy)^{{\delta}-2c-{\ell}-1}{\times}_3F_2\[{^{a,\;b,\;2c+{\ell}+1}_{\frac{1}{2}(a+b+i+1),\;2c+j}}\;;{\frac{(1-x)y}{1-xy}}\]dxdy$$ and $${{\int}^1_0}{{\int}^1_0}\;x^{{\gamma}-1}y^{{\gamma}+c+{\ell}}(1-x)^{c+{\ell}}(1-y)^{c-1}(1-xy)^{{\delta}-2c-{\ell}-1}{\times}_3F_2\[{^{a,\;b,\;2c+{\ell}+1}_{\frac{1}{2}(a+b+i+1),\;2c+j}}\;;{\frac{1-y}{1-xy}}\]dxdy$$ in the most general form for any ${\ell}{\in}{\mathbb{Z}}$ and i, j = 0, ${\pm}1$, ${\pm}2$. The results are derived with the help of generalization of Edwards's well known double integral due to Kim, et al. and generalized classical Watson's summation theorem obtained earlier by Lavoie, et al. More than one hundred ineteresting special cases have also been obtained.

• Toxicological Research
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• v.16 no.2
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• pp.95-100
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• 2000

In previous study, both constitutive expression and 3-methylcholanthrene (3MC)-mediated elevation of CYP1A2 mRNA were demonstrated in human hepatoma HepG2 cells by reverse transcription-polymerase chain reaction (RT-PCR), suggesting that HepG2 cells would be appropriate for the study of human CYP1A2 regulation(Chung and Bresnick, 1994). Further studies were conducted to determine the basis of this induction phenomenon that is observed in HepG2 cells. Since CYP1A1 gene, another polycyclic hydrocarbon(PH)-inducible gene, is regulated by PHs through their interactions via receptors with cis-elements, the 5'-flanking region of human CYP 1A2 gene was analyzed to search such responsive elements. The promoter activity of various lengths of CYP1A2 gene sequence (-3203/+58bp) was measured in transiently-transfected HepG2 cells by fusion constructs containing the CAT, hGH or luciferase genes as a reporter. This region of the CYP1A2 gene, although containing a XRE, was only weakly responsive (less than 2 fold induction) to 10 nM of TCDD or 1 $\mu$M 3 MC treatment. This small enhancement of promoter activity is inconsistent with the previous observation, i.e., 12 to 14 fold-enhanced CYP1A2 mRNA from 1 $\mu$M 3 MC treated HepG2 cells, suggesting that additional mechanisms would exist for PH-mediated induction of CYP1A2 in these cells.

• Journal of Life Science
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• v.22 no.2
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• pp.281-284
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• 2012

This study demonstrated that upregulation of gene expression of endoplasmic reticulum (ER) stress chaperones (Bip, ERp29, calnexin, and PDI), ER stress sensors (PERK, ATF6, and Ire1), and cAMP phosphodiesterase 7A1 (cAMP PDE7A1) was induced by ER stresses in FRTL5 cells. While removing A23187 from the culture medium restored upregulation of cAMP PDE7A1 gene expression, removal of thapsigargin did not recover its expression. In addition, cAMP PDE7A1 gene expression was strongly inhibited by treatment with A23187 combined with thyroid stimulating hormone (TSH). The results are the first to show that ER stress induces cAMP PDE7A1 gene expression.

• Journal of Life Science
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• v.27 no.10
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• pp.1104-1110
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• 2017

SET1A is a histone H3K4 methyltransferase that catalyzes di- and trimethylation of histone H3 at lysine 4 (H3K4). Mono-, di-, and trimethylations on H3K4 (H3K4me1, H3K4me2, and H3K4me3, respectively) are generally correlated with gene activation. Although H3K4 methylation is associated with the stimulation of adipogenesis of 3T3-L1 preadipocytes, it remains unknown whether SET1A plays a role in the regulation of adipogenesis of 3T3-L1 preadipocytes. Here, we investigated whether SET1A regulates 3T3-L1 preadipocytes' adipogenesis and characterized the mechanism involved in this regulation. SET1A expression increased during 3T3-L1 preadipocytes' adipogenesis. Consistent with the increased SET1A expression, the global H3K4me3 level had also increased on day 2 after the induction of adipogenesis in 3T3-L1 adipocytes. SET1A knockdown using siRNA in 3T3-L1 preadipocytes inhibited 3T3-L1 preadipocytes' adipogenesis, as assessed by Oil Red O staining and the expression of adipogenic genes, indicating that SET1A stimulates the adipogenesis of 3T3-L1 preadipocytes. SET1A knockdown inhibited the cell proliferation of 3T3-L1 cells during mitotic clonal expansion (MCE) via down-regulation of the cell cycle gene cyclin E1, as well as the DNA synthesis gene, dihydrofolate reductase. Furthermore, SET1A knockdown repressed peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) expression during the late stage of adipogenesis. These results indicate that SET1A stimulates MCE and $PPAR{\gamma}$ expression, which leads to the promotion of 3T3-L1 preadipocytes' adipogenesis.

• Environmental Mutagens and Carcinogens
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• v.26 no.3
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• pp.86-88
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• 2006

Cytochrome P450 1A2 (CYP1A2) is a xenobiotic metabolizing enzyme that is tissue-specifically expressed in the mammalian liver. In this study, the extent of CYP1A2 promoter methylation was analyzed to determine its potential role in the regulation of CYP1A2 in diethylnitrosamine (DEN)-induced mouse liver tumors. CYP1A2 mRNA was under-expressed about three fold in DEN-induced liver tumors compared to age-matched control livers. The CYP1A2 promoter was hypermethylated in DEN-induced liver tumors compared to controls, especially in a promoter domain close to the coding region. These results suggest that promoter methylation is involved in the regulation of CYP1A2 in mouse liver tumors.

• Journal of applied mathematics & informatics
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• v.40 no.5_6
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• pp.1137-1150
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• 2022

Consider the quantum algebra U_q(sl₂) over field 𝓕 (char(𝓕) = 0) with equitable generators x^±1, y and z, where q is fixed nonzero, not root of unity scalar in 𝓕. Let V denote a finite dimensional irreducible module for this algebra. Let Λ ∈ End(V), and let {A₁, A₂, A₃} = {x, y, z}. First we show that if Λ, A₁ is a Leonard pair, then this Leonard pair have four types, and we show that for each type there exists a Leonard pair Λ, A₁ in which Λ is a linear combination of 1, A₂, A₃, A₂A₃. Moreover, we use Λ to construct 𝚼 ∈ U_q(sl₂) such that 𝚼, A^-1₁ is a Leonard pair, and show that 𝚼 = I + A₁Φ + A₁ΨA₁ where Φ and Ψ are linear combination of 1, A₂, A₃.

• Toxicological Research
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• v.14 no.4
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• pp.587-594
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• 1998

In order to understand the mechanism if the regulation of CYP 1A1 gene expression and ethoxyresorufin deethylase (EROD) activity in ex vivo system, we have studied the action of TCDD and 3MC in the isolated perfused female rat liver. CYP1A1 mRNA level and EROD activity were measured in rat liver that was isolated and perfused with various chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene (3MC), 17$\beta$-estradiol (E$_2$), morin. TCDD or 3MC alone perfusion into female rat liver resulted in increase of CYP 1A1 mRNA level and the magnitude of stimulation was six times higher with TCDD treatment than 3MC treatment. However E$_2$ perfusion into female rat liver showed inhibition of CYP 1A1 mRNA level. When 10$^{-8}$ M E$_2$ was administered concomitantly with either 10$^{-9}$ M TCDD or 10$^{-9}$ M 3MC, stimulated CYP 1A1 mRNA by either TCDD or 3MC was inhibited. Morin was examined for its effects on CYP 1A1 mRNA level and result was similar to that was observed with estrogen. EROD activity was also stimulated with either TCDD or 3MC perfusion, and the magnitude of EROD stiumlation was smaller than that of CYP 1A1 mRNA stimulation in response to TCDD or 3MC perfusion. Unlike CYP1A1 mRNA level, stimulation of EROD activity was greater with 3MC than TCDD. Concomitant perfusion either E$_2$ or morin with TCDD or 3MC inhibited 3MC perfusion or TCDD perfusion stimulated EROD activity. These data suggested that TCDD and 3MC might act diffrently in terms of regulation of CYP 1A1 gene expression in rat liver.

• Journal of Food Hygiene and Safety
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• v.32 no.3
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• pp.171-178
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• 2017

This study evaluated the protective effect of Chungkookjang (CKJ) extract, a Korean traditional fermented soybean product made from Bacillus species in rice straw and boiled soybean, and one of its main flavonoids, genistein, against Trp-P-1 induced cytotoxicity and DNA damage in HepG2 cells. CKJ and genistein exhibited protective effect against Trp-P-1 induced cytotoxicity and Trp-P-1 induced DNA single strand breaks. CKJ and genistein inhibited Trp-P-1 induced CYP1A1 and CYP1A2 transcription in HepG2 cells. Our results indicated that CKJ and genistein have the protective effect against Trp-P-1 induced cytotoxicity and DNA damage. Via inhibiting expression of CYP1A1 and CYP1A2. CKJ can be used as a promising functional food material that prevents the genotoxicity induced by carcinogens produced by the heat treatment of foods such as heterocyclic amines (HCAs) that cause genomic instability.

• Archives of Pharmacal Research
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• v.27 no.2
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• pp.199-205
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• 2004

Cytochrome P450 (P450) 1 enzymes such as P450 1A1, 1A2, and 181 are known to be involved in the oxidative metabolism of various procarcinogens and are regarded as important target enzymes for cancer chemoprevention. Previously, several hydroxystilbene compounds were reported to inhibit P450 1 enzymes and were rated as candidate chemopreventive agents. In this study, we investigated the inhibitory effect of 2-[2-(3,5-dimethoxyphenyl)vinyl]-thiophene (DMPVT), produced from the chemical modification of oxyresveratrol, on the activities of P450 1 enzymes. The inhibitory potential by DMPVT on the P450 1 enzyme activity was evaluated with the Escherichia coli membranes of the recombinant human cytochrome P450 1A1, 1A2, or 1B1 coexpressed with human NADPH-P450 reductase. DMPVT significantly inhibited ethoxyresorufin O-deethylation (EROD) activities with $IC_{50}$ values of 61, 11, and 2 nM for 1A1, 1A2, and 1B1, respectively. The EROO activity in OMBA-treated rat lung microsomes was also significantly inhibited by OMPVT in a dose-dependent manner. The modes of inhibition by DMPVT were non-competitive for all three P450 enzymes. The inhibition of P450 1B1-mediated EROD activity by OMPVT did not show the irreversible mechanism-based effect. The loss of EROD activity in P450 1B1 with OMPVT incubation was not blocked by treatment with the trapping agents such as glutathione, N-acetylcysteine, or dithiothreitol. Taken together, the results suggested DMPVT to be a strong noncompetitive inhibitor of human P450 1 enzymes that should be considered as a good candidate for a cancer chemopreventive agent in humans.