Related Experiment Video

Updated: Jul 10, 2026

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
10:36

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

Novel identification of UDP-glucuronosyltransferase 1A10 as an estrogen-regulated target gene

Athena Starlard-Davenport1, Beverly Lyn-Cook, Anna Radominska-Pandya

  • 1Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

Steroids
|November 6, 2007
PubMed

Insights

Estrogen (E2) up-regulates UGT1A10 mRNA in ER-positive breast cancer cells, then down-regulates it. This estrogen-regulated gene may influence estrogen signaling and clearance in breast cancer.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Background:

  • Uridine 5'-diphospho-glucuronosyltransferase 1A10 (UGT1A10) is involved in inactivating estrogens.
  • Estrogen receptor (ER) signaling plays a critical role in the development and progression of ER-positive breast cancer.

Purpose of the Study:

  • To investigate the regulation of UGT1A10 expression by estrogen (E2) in human breast cancer cell lines.
  • To determine if UGT1A10 is an estrogen-regulated gene in ER-positive breast cancer cells.

Main Methods:

  • MCF-7 (ER-positive) and MDA-MB-231 (ER-negative) breast cancer cell lines were treated with E2.
  • UGT1A10 mRNA levels were analyzed using quantitative real-time PCR.
  • UGT1A10 protein levels and glucuronidation activity were assessed by Western blot and enzymatic assays.
  • The effect of antiestrogen (ICI 182,780) and transcriptional inhibitor (actinomycin-d) on UGT1A10 mRNA expression was evaluated.

Main Results:

  • E2 treatment caused a dose-dependent up-regulation of UGT1A10 mRNA in MCF-7 cells, followed by down-regulation at higher concentrations.
  • E2 did not stimulate UGT1A10 mRNA expression in MDA-MB-231 cells.
  • ICI 182,780 blocked E2-induced UGT1A10 mRNA expression, while actinomycin-d did not.
  • E2 also modulated UGT1A10 protein levels and enzymatic activity in MCF-7 cells.
  • Other estrogenic compounds like PPT and Genistein also stimulated UGT1A10 mRNA expression.

Conclusions:

  • UGT1A10 is a novel, estrogen-regulated target gene in ER-positive human breast cancer cells.
  • The regulation of UGT1A10 mRNA by E2 appears to be mediated through the ER.
  • The observed biphasic regulation of UGT1A10 by E2 may influence estrogen availability and signaling in breast cancer cells.

More Related Videos

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells16:24

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells

Published on: February 21, 2014

Related Concept Videos

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes: