ArticleMolecular endocrinology (Baltimore, Md.)2009
IKKbeta mediates cell shape-induced aromatase expression and estrogen biosynthesis in adipose stromal cells.
Article in Molecular endocrinology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Aromatase expression increases the survival and malignancy of estrogen receptor positive breast cancer cells.PloS one · 2015Article
- Expression of P450arom and Estrogen Receptor Alpha in the Oviduct of Chinese Brown Frog (Rana dybowskii) during Prehibernation.International journal of endocrinology · 2015Article
- Obesity-associated systemic interleukin-6 promotes pre-adipocyte aromatase expression via increased breast cancer cell prostaglandin E2 production.Breast cancer research and treatment · 2015Article
- NSAID use reduces breast cancer recurrence in overweight and obese women: role of prostaglandin-aromatase interactions.Cancer research · 2014Article
- Female adipocyte androgen synthesis and the effects of insulin.Molecular genetics and metabolism reports · 2014Article
- Regulation of adipose oestrogen output by mechanical stress.Nature communications · 2013Article
- Weight gain increases human aromatase expression in mammary gland.Molecular and cellular endocrinology · 2012Article
- Aromatase, breast cancer and obesity: a complex interaction.Trends in endocrinology and metabolism: TEM · 2012Review
- Article
- Aromatase immunoreactivity is increased in mammographically dense regions of the breast.Breast cancer research and treatment · 2011Article
- Cell density-dependent transcriptional activation of endocrine-related genes in human adipose tissue-derived stem cells.Experimental cell research · 2010Article
- Selective synthesis and biological evaluation of sulfate-conjugated resveratrol metabolites.Journal of medicinal chemistry · 2010Article
- Cell density is a critical determinant of aromatase expression in adipose stromal cells.The Journal of steroid biochemistry and molecular biology · 2010Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Aromatase (Cyp19) is a key enzyme in estrogen biosynthesis and an important target in breast cancer therapy. Within tumor microenvironment, tumor cells stimulate aromatase expression in adipose stromal cells (ASCs), which in turn promotes estrogen-dependent growth of estrogen receptor (ER)-positive tumor cells. However, it is not clear how aromatase transcription and estrogen biosynthesis are regulated in ASCs under a precancerous condition. Here we demonstrate that cell shape change alone is sufficient to induce aromatase expression in primary ASCs from cancer-free individuals. The activation of aromatase transcription is mediated by IkappaB kinase-beta (IKKbeta), a kinase previously known for its cancer-promoting activity in tumor cells. Activation of IKKbeta leads to elevated expression of transcription factor CCAAT/enhancer-binding protein-beta (C/EBPbeta), which binds to and stimulates two breast cancer-associated promoters of the aromatase gene. We also show that shape-induced estrogen production in ASCs can stimulate estrogen-dependent transcription in ER-positive breast tumor cells. We suggest that IKKbeta-dependent aromatase induction due to changes in cellular architecture in adipose tissue may contribute to the breast cancer risks associated with high mammagraphic density and obesity.
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