Related Experiment Video
Updated: Jun 27, 2026
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Expression of 17beta-hydroxysteroid dehydrogenases and other estrogen-metabolizing enzymes in different cancer cell
1Faculty of Medicine, Institute of Biochemistry, University of Ljubljana, Ljubljana, Slovenia.
Abstract:
Estrogen action is regulated at the receptor level by regulation of expression of estrogen receptors, and at the pre-receptor level by interconversions between the active hormone (estradiol) and its inactive counterparts (estrone, estrone-sulfate). In peripheral tissues, estrogens can be produced via the aromatase or the sulfatase pathways. Aromatase converts androstenedione and testosterone to estrone and estradiol, respectively, and sulfatase releases estrogens from inactive sulfates, while sulfotransferase catalyzes the reverse reaction. In both pathways, 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) are of paramount importance as they catalyze activation of estrone to estradiol and inactivation of estradiol to estrone. These enzymes belong to either the short-chain dehydrogenase/reductase (SDR) or the aldo-keto reductase (AKR) protein superfamilies. Differential expression of these pre-receptor regulatory enzymes can lead to high estradiol concentrations, which have been implicated in the development of different diseases. Here, we have examined gene expression levels of estrogen-metabolizing enzymes, as six SDRs (17beta-HSD types 1, 2, 4, 7, 8, 12) and one AKR (17beta-HSD type 5; AKR1C3), of aromatase, steroid sulfatase (STS) and estrogen sulfotransferase (SULT1E1), and of the alpha and beta estrogen receptors (ERs), in breast cancer (MCF-7), endometrial cancer (Ishikawa), choriocarcinoma (JEG3) and liver cancer (HepG2) cell lines. After RNA isolation and cDNA synthesis, real-time PCR analyses were performed. The expression of AKR1C3 was examined also at the protein level. Our data show that in all four cancer cell lines, estradiol can be synthesized from estrone by the action of 17beta-HSD type 12, or from estrone-sulfate by sulfatase. In JEG3 and HepG2 cells, estradiol can be formed from androgens by aromatase and 17beta-HSD type 1. Also in HepG2 cells, AKR1C3, which converts androstenedione to testosterone, in concert with aromatase might be responsible for estradiol formation. In MCF7 and Ishikawa cells, estradiol exerts its actions through ERalpha, while in JEG3 and HepG2 cells, it may act through non-ER-mediated pathways.
Insights
Estrogen metabolism enzymes are expressed in various cancer cells, influencing estradiol levels and potentially disease development. These enzymes regulate hormone activation and inactivation, impacting cancer cell signaling pathways.
Area of Science:
- Endocrinology
- Molecular Biology
- Cancer Research
Background:
- Estrogen action is regulated by estrogen receptors (ERs) and pre-receptor metabolism.
- Interconversion of estradiol, estrone, and estrone-sulfate occurs via aromatase, sulfatase, sulfotransferase, and 17beta-hydroxysteroid dehydrogenases (17beta-HSDs).
- Differential expression of these enzymes can lead to elevated estradiol, implicated in various diseases.
Purpose of the Study:
- To examine gene and protein expression of key estrogen-metabolizing enzymes and ERs in four human cancer cell lines.
- To understand the pathways of estradiol synthesis and inactivation within these cancer models.
Main Methods:
- Real-time PCR was used to analyze gene expression of selected 17beta-HSDs (SDR and AKR superfamilies), aromatase, steroid sulfatase (STS), estrogen sulfotransferase (SULT1E1), and ERs.
- Protein expression of AKR1C3 was also assessed.
- Cancer cell lines included breast (MCF-7), endometrial (Ishikawa), choriocarcinoma (JEG3), and liver (HepG2).
Main Results:
- All four cell lines demonstrated pathways for estradiol synthesis from estrone (via 17beta-HSD type 12) or estrone-sulfate (via sulfatase).
- JEG3 and HepG2 cells can produce estradiol from androgens via aromatase and 17beta-HSD type 1.
- MCF7 and Ishikawa cells primarily utilize ERalpha for estradiol action, whereas JEG3 and HepG2 cells may involve non-ER-mediated pathways.
Conclusions:
- Cancer cell lines possess distinct pre-receptor estrogen metabolism pathways.
- The expression patterns of estrogen-metabolizing enzymes and ERs vary across different cancer types.
- These findings highlight the complex regulation of estrogen signaling in cancer and its potential therapeutic implications.