| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Bhardwaj, Priya Du, Baoheng Zhou, Xi Kathy Sue, Erika Giri, Dilip Harbus, Michael D. Falcone, Domenick J. Hudis, Clifford A. Subbaramaiah, Kotha Dannenberg, Andrew J. |
| Description |
Author Affiliation: Bhardwaj P ( Department of Medicine, Weill Cornell Medical College, New York, New York.); Du B ( Department of Medicine, Weill Cornell Medical College, New York, New York.); Zhou XK ( Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, New York.); Sue E ( Department of Medicine, Weill Cornell Medical College, New York, New York.); Giri D ( Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.); Harbus MD ( Department of Medicine, Weill Cornell Medical College, New York, New York.); Falcone DJ ( Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York.); Hudis CA ( Department of Medicine, Weill Cornell Medical College, New York, New York. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.); Subbaramaiah K ( Department of Medicine, Weill Cornell Medical College, New York, New York.); Dannenberg AJ ( Department of Medicine, Weill Cornell Medical College, New York, New York. ajdannen@med.cornell.edu.) |
| Abstract |
Obesity is a risk factor for the development of hormone receptor (HR)-positive breast cancer in postmenopausal women. Obesity causes subclinical inflammation in white adipose tissue (WAT), characterized by macrophages surrounding dead or dying adipocytes forming crown-like structures (CLS). Estrogen synthesis is catalyzed by aromatase. Previously, we demonstrated CLS and elevated levels of proinflammatory mediators and aromatase in the mammary glands of obese mice and breast tissue of obese women. Here, we tested the hypothesis that supplemental estrogen could prevent or reverse WAT inflammation (WATi) and related molecular changes in the mammary gland. C57BL/6J mice were ovariectomized (OVX) to simulate the postmenopausal state. Supplementation with 17ß-estradiol (E2) protected against high fat diet (HFD)-induced weight gain and mammary glands WATi. Expression of proinflammatory mediators (Cox-2, TNF , IL1ß) and aromatase were also reduced in the mammary glands of mice that received supplemental E2. Next, to determine whether E2 supplementation can reverse WATi, obese OVX mice were treated with E2 or placebo and then continued on HFD. E2 supplementation induced weight loss, reversed mammary gland inflammation, and downregulated expression of proinflammatory mediators and aromatase. Finally, we determined whether the protective effects of E2 were mediated by estrogen receptor- (ER ). Knocking out ER in ovary intact mice fed a HFD led to weight gain, WATi and elevated levels of proinflammatory mediators and aromatase mimicking the effects of OVX. Taken together, our findings indicate that estrogen via ER protects against weight gain, WATi and associated increases in proinflammatory mediators and aromatase in the mammary gland. |
| File Format |
HTM / HTML |
| ISSN |
19406207 |
| e-ISSN |
19406215 |
| DOI |
10.1158/1940-6207.CAPR-15-0082 |
| Journal |
Cancer Prevention Research |
| Issue Number |
8 |
| Volume Number |
8 |
| Language |
English |
| Publisher |
American Association for Cancer Research |
| Publisher Date |
2015-08-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Discipline Oncology Estrogens Therapeutic Use Mammary Glands, Animal Drug Effects Mastitis Prevention & Control Obesity Complications Animals Diet, High-fat Adverse Effects Inflammation Mediators Metabolism Pathology Etiology Mice Mice, Inbred C57bl Physiopathology Ovariectomy Rna, Messenger Genetics Real-time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Weight Gain Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cancer Research Oncology |
