ArticleBreast cancer research : BCR2004
Intratumoural mRNA expression of genes from the oestradiol metabolic pathway and clinical and histopathological parameters of breast cancer.
Article in Breast cancer research : BCR, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Influence of CYP19A1 gene expression levels in women with breast cancer: a systematic review of the literature.Clinics (Sao Paulo, Brazil)Pooled it
- Steroid Sulphatase and Its Inhibitors: Past, Present, and Future.Molecules (Basel, Switzerland) · 2021Review
- Review
- CYP19A1 gene expression in the peripheral blood of Brazilian women with breast cancer relapse.BMC cancer · 2020Article
- Elevated Aromatase (CYP19A1) Expression Is Associated with a Poor Survival of Patients with Estrogen Receptor Positive Breast Cancer.Hormones & cancer · 2018Article
- The in vitro effects of 2-methoxyestradiol-bis-sulphamate on cell numbers, membrane integrity and cell morphology, and the possible induction of apoptosis and autophagy in a non-tumorigenic breast epithelial cell line.Cellular & molecular biology letters · 2010Article
- Update information on drug metabolism systems--2009, part II: summary of information on the effects of diseases and environmental factors on human cytochrome P450 (CYP) enzymes and transporters.Current drug metabolism · 2010Review
- Alternative use of multiple exons 1 of aromatase gene in cancerous and normal breast tissues from women over the age of 80 years.Breast cancer research : BCR · 2009Article
- A review of coumarin derivatives in pharmacotherapy of breast cancer.Current medicinal chemistry · 2008Review
- Pharmacokinetics of the nonsteroidal steroid sulphatase inhibitor 667 COUMATE and its sequestration into red blood cells in rats.British journal of cancer · 2004Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe expression of the oestrogen receptor (ER) is one of the more important clinical parameters of breast cancer. However, the relationship between the ER and its ligand, oestradiol, and the enzymes that synthesise it are not well understood. The expression of mRNA transcripts of members of the oestradiol metabolic and signalling pathways including the ER was studied in detail.
methodmRNA transcripts for aromatase (CYP19), 17-beta-hydroxysteroid dehydrogenase I, 17-beta-hydroxysteroid dehydrogenase II, ERalpha, ERbeta, steroid sulfatase (STS), oestradiol sulfotransferase (EST), cyclin D1 (CYCLD1) and ERBB2 were fluorometrically quantified by competitive RT-PCR using an internal standard in 155 breast carcinomas. In addition, the transcripts of CYP19 were analysed for alternative splicing/usage of exon 1 and an alternative poly A tail.
resultsA great variability of expression was observed, ranging from 0 to 2376 amol/mg RNA. The highest levels were observed for STS and EST, and the lowest levels (close to zero) were observed for the 17-beta-hydroxysteroid dehydrogenase isoenzymes. The levels of mRNA expression were analysed with respect to clinical and histopathological parameters as well as for disease-free survival. High correlation of the mRNA expression of STS, EST and 17-beta-hydroxysteroid dehydrogenase in the tumours suggested a common regulation, possibly by their common metabolite (oestradiol). Hierarchical clustering analysis in the 155 patients resulted in two main clusters, representing the ERalpha-negative and ERalpha-positive breast cancer cases. The mRNA expression of the oestradiol metabolising enzymes did not follow the expression of the ERalpha in all cases, leading to the formation of several subclasses of tumours. Patients with no expression of CYP19 and patients with high levels of expression of STS had significantly shorter disease-free survival time (P > 0.0005 and P < 0.03, respectively). Expression of ERbeta mRNA was a better prognostic factor than that of ERalpha in this material.
conclusionOur results indicate the importance of CYP19 and the enzymes regulating the oestrone sulfate metabolism as factors of disease-free survival in breast cancer, in addition to the well-known factors ER and ERBB2.
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