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Aromatase and breast cancer
1Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA. schen@ smtplink. coh.org
Frontiers in Bioscience : a Journal and Virtual Library
|August 11, 1998
Summary
Aromatase enzyme (CYP19) drives estrogen production in breast cancer. Inhibiting this enzyme, through therapies or diet, offers a strategy to reduce cancer growth and incidence.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Estrogens are crucial in breast cancer development.
- Aromatase (CYP19) synthesizes estrogens and is upregulated in breast cancer tissue.
- Estrogen produced in situ within tumors promotes breast cancer growth.
Purpose of the Study:
- To investigate the role of aromatase in breast cancer.
- To explore aromatase promoter regulation in normal versus cancerous tissue.
- To evaluate aromatase inhibitors and phytoestrogens for breast cancer prevention and treatment.
Main Methods:
- Enzyme activity assays, immunocytochemistry, and RT-PCR analysis.
- Cell culture and animal models, including transgenic mice.
- Computer modeling, site-directed mutagenesis, and inhibition kinetics.
Main Results:
- Aromatase expression and activity are elevated in breast cancer.
- Tumor aromatase promotes growth via autocrine and paracrine mechanisms.
- Aromatase promoter activity shifts from glucocorticoid to cAMP stimulation in cancer.
- Aromatase inhibitors show efficacy in a subset of patients resistant to anti-estrogen therapy.
- Phytoestrogens like flavones and isoflavones interact differently with aromatase.
Conclusions:
- Targeting in situ estrogen biosynthesis via aromatase inhibition is a viable breast cancer strategy.
- Understanding aromatase regulation and inhibitor interactions can guide therapeutic and dietary interventions.
- Dietary phytoestrogens may play a role in reducing breast cancer incidence by modulating estrogen production.