Expression and Inducibility of UDP-glucuronosyltransferase 1As in MCF-7 Human Breast Carcinoma Cells

Nobumitsu Hanioka, Hiroyuki Iwabu, Hiroyuki Hanafusa, Shintaro Nakada, Shizuo Narimatsu

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)253-258
Number of pages6
JournalBasic and Clinical Pharmacology and Toxicology
Volume110
Issue number3
DOIs
Publication statusPublished - Mar 2012

Fingerprint

Glucuronosyltransferase
MCF-7 Cells
irinotecan
Cells
Breast Neoplasms
Messenger RNA
Estrogen Receptors
Aryl Hydrocarbon Receptor Nuclear Translocator
Hymecromone
Tissue
Aryl Hydrocarbon Receptors
Polymerase chain reaction
Glucocorticoid Receptors
Transcription
Phenobarbital
Dexamethasone
Toxicity
Serotonin
Protein Isoforms
Microsomes

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Expression and Inducibility of UDP-glucuronosyltransferase 1As in MCF-7 Human Breast Carcinoma Cells. / Hanioka, Nobumitsu; Iwabu, Hiroyuki; Hanafusa, Hiroyuki; Nakada, Shintaro; Narimatsu, Shizuo.

In: Basic and Clinical Pharmacology and Toxicology, Vol. 110, No. 3, 03.2012, p. 253-258.

Research output: Contribution to journalArticle

Hanioka, Nobumitsu ; Iwabu, Hiroyuki ; Hanafusa, Hiroyuki ; Nakada, Shintaro ; Narimatsu, Shizuo. / Expression and Inducibility of UDP-glucuronosyltransferase 1As in MCF-7 Human Breast Carcinoma Cells. In: Basic and Clinical Pharmacology and Toxicology. 2012 ; Vol. 110, No. 3. pp. 253-258.
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