Expression and inducibility of UDP-glucuronosyltransferase 1As in MCF-7 human breast carcinoma cells. 2012

Nobumitsu Hanioka, and Hiroyuki Iwabu, and Hiroyuki Hanafusa, and Shintaro Nakada, and Shizuo Narimatsu
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama, Japan. nhanioka@cc.okayama-u.ac.jp

UDP-glucuronosyltransferases (UGTs) are conjugation enzymes, which are regulated in a tissue-specific manner by endogenous and environmental factors. In this study, we focused on UGT1A isoforms broadly expressed in hepatic and extrahepatic tissues and examined the expression and inducibility of UGT1As (UGT1A1 and UGT1A3-1A10) in MCF-7 cells (human breast carcinoma cell line). Reverse transcription polymerase chain reaction (RT-PCR) analysis demonstrated that UGT1A1, UGT1A6 and UGT1A9 mRNAs as well as the mRNAs of transcriptional regulators (AhR, aryl hydrocarbon receptor; Arnt, AhR nuclear translocator; ERα, oestrogen receptor α; ERβ, oestrogen receptor β; and GR, glucocorticoid receptor) are expressed in MCF-7 cells. UGT1A6 mRNA level in MCF-7 cells was significantly increased to 1.9 times by β-naphthoflavone (BNF), whereas UGT1A1 and UGT1A9 mRNA levels were not affected by BNF. There were no significant changes in the mRNAs of UGT1A1, UGT1A6 and UGT1A9 in MCF-7 cells by treatment with phenobarbital (PB) and dexamethasone (DEX) in MCF-7 cells. The kinetics of 7-ethyl-10-hydroxycamptothecin (SN-38), 5-hydroxytryptamine (5-HT) and 4-methylumbelliferone (4-MU) glucuronidation by microsomes from control and BNF-treated MCF-7 cells fitted with the Michaelis-Menten model, and the V(max) and CL(int) values were significantly increased to 7.5-8.5 times and 5.9-10.4 times by BNF treatment, respectively. These findings suggest that BNF induces UGT1A6 in MCF-7 cells and that the increase may be mediated by AhR but not pregnane X receptor (PXR)/constitutive androstane receptor (CAR). The information gained in this study should help predict and assess the toxicity of environmental chemicals.

UI MeSH Term Description Entries
D008861 Microsomes Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) Microsome
D010634 Phenobarbital A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D003907 Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D004790 Enzyme Induction An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. Induction, Enzyme
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014453 Glucuronosyltransferase A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 2.4.1.17. Glucuronyltransferase,UDP Glucuronosyltransferase,17 beta-Hydroxysteroid UDP-Glucuronosyltransferase,4-Nitrophenol-UDP-Glucuronosyltransferase,7-Hydroxycoumarin UDP Glucuronyltransferase,Androsterone UDP-Glucuronosyltransferase,Bilirubin UDP-Glucuronyltransferase,Estrogen UDP-Glucuronosyltransferase,Estrone Glucuronyltransferase,Glucuronic Transferase,Morphine Glucuronyltransferase,UDP Glucuronyl Transferase,UDP-Glucuronic Acid 3-O-beta-D-Galactosyl-D-Galactose Glucuronosyltransferase,p-Nitrophenyl UDP-Glucuronosyltransferase,17 beta Hydroxysteroid UDP Glucuronosyltransferase,4 Nitrophenol UDP Glucuronosyltransferase,7 Hydroxycoumarin UDP Glucuronyltransferase,Androsterone UDP Glucuronosyltransferase,Bilirubin UDP Glucuronyltransferase,Estrogen UDP Glucuronosyltransferase,Glucuronosyltransferase, UDP,Glucuronyl Transferase, UDP,Glucuronyltransferase, 7-Hydroxycoumarin UDP,Glucuronyltransferase, Estrone,Glucuronyltransferase, Morphine,Transferase, Glucuronic,Transferase, UDP Glucuronyl,UDP Glucuronic Acid 3 O beta D Galactosyl D Galactose Glucuronosyltransferase,UDP Glucuronyltransferase, 7-Hydroxycoumarin,UDP-Glucuronosyltransferase, 17 beta-Hydroxysteroid,UDP-Glucuronosyltransferase, Androsterone,UDP-Glucuronosyltransferase, Estrogen,UDP-Glucuronosyltransferase, p-Nitrophenyl,UDP-Glucuronyltransferase, Bilirubin,p Nitrophenyl UDP Glucuronosyltransferase
D015971 Gene Expression Regulation, Enzymologic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis. Enzymologic Gene Expression Regulation,Regulation of Gene Expression, Enzymologic,Regulation, Gene Expression, Enzymologic

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