Increased levels of COX-2 and prostaglandin E2 contribute to elevated aromatase expression in inflamed breast tissue of obese women.

Cancer Discovery
Kotha SubbaramaiahAndrew J Dannenberg

Abstract

Obesity is a risk factor for hormone receptor-positive breast cancer in postmenopausal women. Estrogen synthesis is catalyzed by aromatase, which is encoded by CYP19. We previously showed that aromatase expression and activity are increased in the breast tissue of overweight and obese women in the presence of characteristic inflammatory foci [crown-like structures of the breast (CLS-B)]. In preclinical studies, proinflammatory prostaglandin E(2) (PGE(2)) is a determinant of aromatase expression. We provide evidence that cyclooxygenase (COX)-2-derived PGE(2) stimulates the cyclic AMP (cAMP) → PKA signal transduction pathway that activates CYP19 transcription, resulting in increased aromatase expression and elevated progesterone receptor levels in breast tissues from overweight and obese women. We further demonstrate that a measure of in-breast inflammation (CLS-B index) is a better correlate of these biologic end points than body mass index. The obesity → inflammation → aromatase axis is likely to contribute to the increased risk of hormone receptor-positive breast cancer and the worse prognosis of obese patients with breast cancer. We show that obesity-associated inflammatory foci in the human breast are associated with elevate...Continue Reading

References

Apr 5, 2001·American Journal of Physiology. Endocrinology and Metabolism·P A KernG Ranganathan
Feb 5, 2002·Annual Review of Physiology·Evan R SimpsonMargaret Jones
Feb 19, 2002·The Journal of Steroid Biochemistry and Molecular Biology·A M BrodieJ H Thijssen
Mar 20, 2002·The Journal of Biological Chemistry·Kotha SubbaramaiahAndrew J Dannenberg
Dec 18, 2003·The Journal of Clinical Investigation·Stuart P WeisbergAnthony W Ferrante
Dec 18, 2003·The Journal of Clinical Investigation·Haiyan XuHong Chen
Jan 7, 2004·Cancer Cell·Andrew J Dannenberg, Kotha Subbaramaiah
May 27, 2004·JAMA : the Journal of the American Medical Association·Mary Beth TerryAlfred I Neugut
Feb 3, 2005·The Journal of Clinical Endocrinology and Metabolism·Edgar S Díaz-CruzRobert W Brueggemeier
Sep 1, 2006·The New England Journal of Medicine·Monica M BertagnolliUNKNOWN APC Study Investigators
Mar 20, 2008·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Alana G HudsonJoel L Weissfeld
Oct 30, 2008·The Journal of Clinical Endocrinology and Metabolism·Salama A SalamaRaj Kumar
Apr 18, 2009·Endocrinology·Margot P Cleary, Michael E Grossmann
Aug 15, 2009·The Journal of Biological Chemistry·Rosa SirianniVincenzo Pezzi
Sep 17, 2009·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Rob C M van KruijsdijkFrank L J Visseren
Feb 13, 2010·Annual Review of Physiology·Jerrold M Olefsky, Christopher K Glass
Apr 3, 2010·Journal of Leukocyte Biology·Takayoshi Suganami, Yoshihiro Ogawa
Aug 11, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Stephen D Hursting, Nathan A Berger
Mar 5, 2011·Cancer Prevention Research·Kotha SubbaramaiahAndrew J Dannenberg
May 31, 2011·Cancer Prevention Research·Patrick G MorrisAndrew J Dannenberg
Jun 7, 2011·The New England Journal of Medicine·Paul E GossUNKNOWN NCIC CTG MAP.3 Study Investigators
Aug 16, 2011·Cancer Research·Edgar S Díaz-CruzPriscilla A Furth

❮ Previous
Next ❯

Citations

Oct 12, 2012·Breast Cancer Research and Treatment·Caroline DiorioEric Vachon
Oct 31, 2013·Journal of Mammary Gland Biology and Neoplasia·Linda Vona-Davis, David P Rose
Nov 14, 2013·Journal of Mammary Gland Biology and Neoplasia·Rishi JainJoseph A Sparano
Oct 5, 2012·Cancer Prevention Research·Stephen D HurstingNathan A Berger
Oct 9, 2012·Cancer Prevention Research·Ofer MargalitRaymond N Dubois
Jun 27, 2013·Nutrition Journal·Khanh vinh quốc Lu'o'ng, Lan Thi Hoàng Nguyễn
Apr 10, 2013·Breast Cancer Research : BCR·Nirukshi U SamarajeewaKristy A Brown
May 30, 2013·American Society of Clinical Oncology Educational Book·Neil M IyengarAndrew J Dannenberg
Jul 6, 2014·Breast Cancer Research and Treatment·Yong CuiWei Zheng
Jun 18, 2014·Journal of Mammary Gland Biology and Neoplasia·Kristy A Brown
Feb 23, 2013·Cancer Prevention Research·Priya BhardwajAndrew J Dannenberg
Sep 28, 2013·Current Breast Cancer Reports·Neil M IyengarAyca Gucalp
Feb 13, 2015·Molecular Medicine Reports·Qing ZhangBin Li
Jan 15, 2015·Annual Review of Medicine·Neil M IyengarAndrew J Dannenberg
Mar 13, 2016·Seminars in Oncology·Ayca GucalpAndrew J Dannenberg
Mar 22, 2016·NPJ Breast Cancer·Carly Bess WilliamsAdam C Soloff
Apr 30, 2013·Prostaglandins & Other Lipid Mediators·Louise R HoweAndrew J Dannenberg
Mar 13, 2016·Seminars in Oncology·Iván P UrayPowel H Brown
Dec 20, 2015·Reproductive Biology and Endocrinology : RB&E·Nicole S CarlsonK Joseph Hurt
Jul 22, 2015·Journal of Mammary Gland Biology and Neoplasia·Honor J HugoE W Thompson
Apr 8, 2015·Steroids·Jiehan LiVeera Vihma
Nov 3, 2015·Biochemical and Biophysical Research Communications·Shankar SumanYogeshwer Shukla
Apr 25, 2013·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·R LopezR Lakshmanaswamy
Mar 7, 2014·International Journal of Cancer. Journal International Du Cancer·Andrea MarkkulaHelena Jernström
Apr 8, 2016·Cancer Treatment Reviews·Maria Vittoria DieciValentina Guarneri
Jul 26, 2015·The Journal of Steroid Biochemistry and Molecular Biology·Xuyi WangKristy A Brown
Aug 3, 2013·Cell Cycle·Levy Kopelovich, Brittney Shea-Herbert
Mar 26, 2014·Oncogene·A G BeristainR Khokha
Mar 30, 2016·Endocrine Journal·Keely May McNamaraHironobu Sasano
Jun 10, 2016·British Journal of Cancer·Mia PerssonHelena Jernström

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.