Abstract
All-trans-retinoic acid has been shown to have an antiproliferative effect in the estrogen receptor alpha-positive breast cancer cell line MCF-7. The mechanism of this effect is not well understood. We have previously shown that 17beta-estradiol down-regulates the basic helix-loop-helix factor Hairy and Enhancer of Split homologue-1 in MCF-7 and T47D cells (Ström, A., Arai, N., Leers, J., and Gustafsson, J. A. (2000) Oncogene 19, 5951-5953) and that this down-regulation is essential for proliferation in response to 17beta-estradiol. Treatment of the same cells with all-trans-retinoic acid prevented 17beta-estradiol-mediated down-regulation of the factor. The antiproliferative effect of all-trans-retinoic acid correlated well with the prevention of Hairy and Enhancer of Split homologue-1 down-regulation. Increasing concentrations of all-trans-retinoic acid, in the range of 1-1000 nm, produced a dose-dependent inhibition of proliferation and prevented 17beta-estradiol-mediated down-regulation of Hairy and Enhancer of Split homologue-1. By using a receptor-specific ligand we were able to show that the retinoic acid receptor alpha is important for regulation of the Hairy and Enhancer of Split homologue-1. Expression of a dominant negative form of Hairy and Enhancer of Split homologue-1 in MCF-7 cells abolished the growth-inhibitory effect of all-trans-retinoic acid in these cells. This finding indicates that Hairy and Enhancer of Split homologue-1 is a mediator of the antiproliferative effect of all-trans-retinoic acid in estrogen receptor alpha-positive breast cancer cell lines.
Keywords
MCF-7Retinoic acidChemistryCancer researchBreast cancerCell cultureInternal medicineCancer cell linesOncologyCancerHuman breastBiologyMedicineBiochemistryCancer cellGeneticsGene
MeSH Terms
AnimalsBasic Helix-Loop-Helix Transcription FactorsBlottingWesternCOS CellsCell DivisionCell LineDose-Response RelationshipDrugDown-RegulationEstradiolGenesDominantHomeodomain ProteinsHumansPrecipitin TestsRNAMessengerReceptorsRetinoic AcidRetinoic Acid Receptor alphaReverse Transcriptase Polymerase Chain ReactionTranscription Factor HES-1TranscriptionGeneticTransfectionTretinoinTumor CellsCultured
Affiliated Institutions
Related Publications
Estrogen receptor status in breast cancer is associated with remarkably distinct gene expression patterns.
To investigate the phenotype associated with estrogen receptor alpha (ER) expression in breast carcinoma, gene expression profiles of 58 node-negative breast carcinomas discorda...
Connective Tissue Growth Factor Induces Apoptosis in Human Breast Cancer Cell Line MCF-7
Connective tissue growth factor (CTGF) is a member of an emerging CCN gene family that is implicated in various diseases associated with fibro-proliferative disorder including s...
Mechanisms of transactivation by retinoic acid receptors
Abstract Retinoids play an important role in development and differentiation (1,2) . Their effect is mediated through nuclear receptors, RAR (α, β and γ) and RXR (α, β and γ), A...
Sequence and Expression of Human Estrogen Receptor Complementary DNA
The mechanism by which the estrogen receptor and other steroid hormone receptors regulate gene expression in eukaryotic cells is not well understood. In this study, a complement...
Both retinoic-acid-receptor- and retinoid-X-receptor-dependent signalling pathways mediate the induction of the brown-adipose-tissue-uncoupling-protein-1 gene by retinoids
The intracellular pathways and receptors mediating the effects of retinoic acid (RA) on the brown-fat-uncoupling-protein-1 gene (ucp-1) have been analysed. RA activates transcri...
Publication Info
- Year
- 2002
- Type
- article
- Volume
- 277
- Issue
- 32
- Pages
- 28376-28379
- Citations
- 48
- Access
- Closed
External Links
Social Impact
Altmetric
PlumX Metrics
Social media, news, blog, policy document mentions
Citation Metrics
48
OpenAlex
1
Influential
36
CrossRef
Cite This
Patrick Müller,
Silke Kietz,
Jan-Ακε Gustafsson
et al.
(2002).
The Anti-estrogenic Effect of All-trans-retinoic Acid on the Breast Cancer Cell Line MCF-7 Is Dependent on HES-1 Expression.
Journal of Biological Chemistry
, 277
(32)
, 28376-28379.
https://doi.org/10.1074/jbc.c200340200
Identifiers
- DOI
- 10.1074/jbc.c200340200
- PMID
- 12080040