Adiposity Results in Metabolic and Inflammation Differences in Premenopausal and Postmenopausal Women Consistent with the Difference in Breast Cancer Risk

H. Zhao, J. Wang, D. Fang, O. Lee, R. T. Chatterton, Vered Stearns, S. A. Khan, S. E. Bulun

Research output: Contribution to journalArticle

Abstract

Obesity is associated with increased risk of breast cancer in postmenopausal but not in premenopausal women. Many factors may be responsible for this difference. The aim of this study was to determine the mechanisms by which the genes related to the AMPK pathway, inflammation, and estrogen actions are affected by adiposity in breast tissue with the objective of identifying differences that may explain the different breast cancer risk in premenopausal and postmenopausal women. Random fine needle aspirates (rFNAs) of breast tissue were collected from 57 premenopausal and 55 postmenopausal women and were classified as normal weight, overweight, or obese. Expression levels of 21 target genes were determined using a TaqMan Low Density Array procedure. Breast tissue estradiol levels were measured by a liquid chromatography-tandem mass spectrometry procedure, and serum estradiol and follicle-stimulating hormone (FSH) were measured by a radioimmunoassay and an enzyme-linked immunosorbent assay, respectively. We found that in postmenopausal women, serum and tissue estradiol levels were increased in those who were overweight, and serum FSH levels were decreased in obese status. Interestingly, RPS6KB1, an AMPK downstream-responsive gene for protein synthesis and cell growth, and estrogen receptor α (encoded by the ESR1 gene) and its target gene GATA3 were significantly decreased in rFNA of premenopausal, obese women. In postmenopausal women, RPS6KB1, ESR1, and GATA3 expression remained unchanged in relation to adiposity. However, prostaglandin-endoperoxide synthase 2 (PTGS2), cyclin D1 (CCND1), and another ESR1 target gene, TFF1, were elevated in rFNA of obese postmenopausal women. Thus, as bodyweight increases, gene expression is indicative of increased proliferation in postmenopausal women but decreased proliferation in premenopausal women. Overall, our data reveal a novel process by which obesity promotes the risk of breast cancer in postmenopausal but not premenopausal women.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalHormones and Cancer
DOIs
StateAccepted/In press - Mar 15 2018

Fingerprint

Adiposity
Breast Neoplasms
Inflammation
Needles
Estradiol
AMP-Activated Protein Kinases
Breast
Genes
Follicle Stimulating Hormone
Obesity
Serum
Cyclin D1
Prostaglandin-Endoperoxide Synthases
Tandem Mass Spectrometry
Liquid Chromatography
Estrogen Receptors
Radioimmunoassay
Estrogens
Enzyme-Linked Immunosorbent Assay
Gene Expression

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cancer Research

Cite this

Adiposity Results in Metabolic and Inflammation Differences in Premenopausal and Postmenopausal Women Consistent with the Difference in Breast Cancer Risk. / Zhao, H.; Wang, J.; Fang, D.; Lee, O.; Chatterton, R. T.; Stearns, Vered; Khan, S. A.; Bulun, S. E.

In: Hormones and Cancer, 15.03.2018, p. 1-11.

Research output: Contribution to journalArticle

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