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Cited by 85Estrogen and related hormone effectsBreast Cancer Treatment StudiesCancer, Lipids, and Metabolism

Aromatase excess in cancers of breast, endometrium and ovary

Open access
Bulun, Serdar E., Chen, Dong, Lu, Meiling, Zhao, Hong, Cheng, Youhong, Demura, Masashi, Yilmaz, Bertan, Martin, Regina +14 more·2007·The Journal of Steroid Biochemistry and Molecular Biology
DOI 10.1016/j.jsbmb.2007.05.027PMC PMC2766613
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Abstract

Pathogenesis and growth of three common women's cancers (breast, endometrium and ovary) are linked to estrogen. A single gene encodes the key enzyme for estrogen biosynthesis named aromatase, inhibition of which effectively eliminates estrogen production in the entire body. Aromatase inhibitors successfully treat breast cancer, whereas their roles in endometrial and ovarian cancers are less clear. Ovary, testis, adipose tissue, skin, hypothalamus and placenta express aromatase normally, whereas breast, endometrial and ovarian cancers overexpress aromatase and produce local estrogen exerting paracrine and intracrine effects. Tissue-specific promoters distributed over a 93-kb regulatory region upstream of a common coding region alternatively control aromatase expression. A distinct set of transcription factors regulates each promoter in a signaling pathway- and tissue-specific manner. In cancers of breast, endometrium and ovary, aromatase expression is primarly regulated by increased activity of the proximally located promoter I.3/II region. Promoters I.3 and II lie 215 bp from each other and are coordinately stimulated by PGE(2) via a cAMP-PKA-dependent pathway. In breast adipose fibroblasts exposed to PGE(2) secreted by malignant epithelial cells, PKC is also activated, and this potentiates cAMP-PKA-dependent induction of aromatase. Thus, inflammatory substances such as PGE(2) may play important roles in inducing local production of estrogen that promotes tumor growth.

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Crossref · 10.1016/j.jsbmb.2007.05.027

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  • In cancers of the breast, endometrium and ovary, CYP19A1 expression is primarily regulated by increased activity of the I.3/II promoter region, which can be upregulated by prostaglandins such as PGE2.

    “Notably, Bulun and colleagues have found that in cancers of breast, endometrium and ovary, expression is primarily regulated by increased activity of the I.3/II promoter region, which can be upregulated by prostaglandins such as PGE2, providing a link between the overexpression of PGs that has been reported to occur in EC [79] and intracrine oestrogen biosynthesis [80].”

    From Endometrial Intracrinology: Oestrogens, Androgens and Endometrial Disorders (2018) · cites this paper as [80]

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Authors
Bulun, S. E., Chen, D., Lu, M., Zhao, H., Cheng, Y., Demura, M., Yilmaz, B., Martin, R., Utsunomiya, H., Thung, S., Su, E., Marsh, E., Hakim, A., Yin, P., Ishikawa, H., Amin, S., Imir, G., Gurates, B., Attar, E., Reierstad, S., Innes, J., & Lin, Z.
Affiliations
Northwestern University (US)
Corresponding author
Bulun, Serdar E.
ORCID
Venue
The Journal of Steroid Biochemistry and Molecular Biology
Publisher
Elsevier BV
Published
2007-08
Volume
106
Issue
1-5
Pages
81-96
ISSN
0960-0760 (ISSN-L)
DOI
10.1016/j.jsbmb.2007.05.027
PMC
PMC2766613
OpenAlex
W2016181677
Cited by
85
References
8
Citations by year
2026: 1 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 7 · 2018: 3 · 2016: 5 · 2015: 8 · 2014: 6 · 2013: 9 · 2012: 8
FWCI
2.69
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (R29CA067167, R01CA067167, CA-67167)
  • Fogarty International Center (R03TW001339)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD046260, U54HD040093, HD-38691, R01HD038691, HD46260, R37HD038691)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
aromatase, breast cancer, endometrial cancer, ovarian cancer, estrogen synthesis, aromatase inhibitors, tissue-specific promoters, prostaglandin E2, cAMP/PKA signaling, protein kinase C, tumor growth, inflammation
MeSH terms
Animals, Aromatase, Breast Neoplasms, Female, Humans, Ovarian Neoplasms, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Endometrial Neoplasms

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