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DOI: 10.1055/s-0035-1552581
Estrogens, Obesity, Inflammation, and Breast Cancer—What Is the Link?
Publikationsverlauf
Publikationsdatum:
02. Juni 2015 (online)

Abstract
It gives me great pleasure to contribute to this special issue of Seminars which honors the career of Bruce Carr. As it happens, Bruce was my first Fellow upon my arrival at the Green Center for Reproductive Biology Sciences at UT Southwestern Medical Center in 1977. At that time, the Center was filled with luminaries of Reproductive Endocrinology, such as John Porter, Jack Johnston, Norman Gant, and of course the Director, Paul MacDonald, so to be given the responsibility of mentoring a new Fellow was a daunting responsibility. However, Bruce quickly rolled up his sleeves and plunged straight in, and we forged a relationship which led to some 36 manuscripts in 4 years. The first of these was entitled “The Role of Serum Lipoproteins in Steroidogenesis by the Human Fetal Adrenal Cortex,” published in the Journal of Clinical Endocrinology and Metabolism, volume 49, pages 146–148, in 1979, and the authors were Simpson ER, Carr BR, Parker CR Jr, Milewich L, Porter JC, and MacDonald PC. Bruce quickly moved up the ranks of the Obstetrics/Gynecology Department to become full Professor and we went our separate ways professionally, but we remain close friends to this day. This special issue is indeed a worthy tribute to an outstanding career and especially to Bruce's role as editor-in-chief of Seminars which he has guided through the rapid evolution of the specialty, always maintaining a strong research focus and thus carrying on the rich tradition of the Green Center and the Obstetrics/Gynecology Department.
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References
- 1 Simpson ER, Clyne C, Rubin G , et al. Aromatase—a brief overview. Annu Rev Physiol 2002; 64: 93-127
- 2 Simpson ER, Misso M, Hewitt KN , et al. Estrogen—the good, the bad, and the unexpected. Endocr Rev 2005; 26 (3) 322-330
- 3 Bulun SE, Price TM, Aitken J, Mahendroo MS, Simpson ER. A link between breast cancer and local estrogen biosynthesis suggested by quantification of breast adipose tissue aromatase cytochrome P450 transcripts using competitive polymerase chain reaction after reverse transcription. J Clin Endocrinol Metab 1993; 77 (6) 1622-1628
- 4 Labrie F, Luu-The V, Labrie C , et al. Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone. Endocr Rev 2003; 24 (2) 152-182
- 5 Agarwal VR, Bulun SE, Leitch M, Rohrich R, Simpson ER. Use of alternative promoters to express the aromatase cytochrome P450 (CYP19) gene in breast adipose tissues of cancer-free and breast cancer patients. J Clin Endocrinol Metab 1996; 81 (11) 3843-3849
- 6 Harada N, Utsumi T, Takagi Y. Tissue-specific expression of the human aromatase cytochrome P-450 gene by alternative use of multiple exons 1 and promoters, and switching of tissue-specific exons 1 in carcinogenesis. Proc Natl Acad Sci U S A 1993; 90 (23) 11312-11316
- 7 Zhou C, Zhou D, Esteban J , et al. Aromatase gene expression and its exon I usage in human breast tumors. Detection of aromatase messenger RNA by reverse transcription-polymerase chain reaction. J Steroid Biochem Mol Biol 1996; 59 (2) 163-171
- 8 Zhao Y, Agarwal VR, Mendelson CR, Simpson ER. Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene. Endocrinology 1996; 137 (12) 5739-5742
- 9 Richards JA, Brueggemeier RW. Prostaglandin E2 regulates aromatase activity and expression in human adipose stromal cells via two distinct receptor subtypes. J Clin Endocrinol Metab 2003; 88 (6) 2810-2816
- 10 Clyne CD, Speed CJ, Zhou J, Simpson ER. Liver receptor homologue-1 (LRH-1) regulates expression of aromatase in preadipocytes. J Biol Chem 2002; 277 (23) 20591-20597
- 11 Zhou J, Suzuki T, Kovacic A , et al. Interactions between prostaglandin E(2), liver receptor homologue-1, and aromatase in breast cancer. Cancer Res 2005; 65 (2) 657-663
- 12 Safi R, Kovacic A, Gaillard S , et al. Coactivation of liver receptor homologue-1 by peroxisome proliferator-activated receptor gamma coactivator-1alpha on aromatase promoter II and its inhibition by activated retinoid X receptor suggest a novel target for breast-specific antiestrogen therapy. Cancer Res 2005; 65 (24) 11762-11770
- 13 Schoonjans K, Dubuquoy L, Mebis J , et al. Liver receptor homolog 1 contributes to intestinal tumor formation through effects on cell cycle and inflammation. Proc Natl Acad Sci U S A 2005; 102 (6) 2058-2062
- 14 The World Cancer Research Fund Expert Report on Obesity and Cancer, November 1, 2007
- 15 Cleland WH, Mendelson CR, Simpson ER. Effects of aging and obesity on aromatase activity of human adipose cells. J Clin Endocrinol Metab 1985; 60 (1) 174-177
- 16 Bulun SE, Simpson ER. Competitive reverse transcription-polymerase chain reaction analysis indicates that levels of aromatase cytochrome P450 transcripts in adipose tissue of buttocks, thighs, and abdomen of women increase with advancing age. J Clin Endocrinol Metab 1994; 78 (2) 428-432
- 17 Ahn J, Schatzkin A, Lacey Jr JV , et al. Adiposity, adult weight change, and postmenopausal breast cancer risk. Arch Intern Med 2007; 167 (19) 2091-2102
- 18 Harvie M, Hooper L, Howell AH. Central obesity and breast cancer risk: a systematic review. Obes Rev 2003; 4 (3) 157-173
- 19 McInnes KJ, Corbould A, Simpson ER, Jones ME. Regulation of adenosine 5′,monophosphate-activated protein kinase and lipogenesis by androgens contributes to visceral obesity in an estrogen-deficient state. Endocrinology 2006; 147 (12) 5907-5913
- 20 Yamauchi T, Kamon J, Minokoshi Y , et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2002; 8 (11) 1288-1295
- 21 Cederroth CR, Vinciguerra M, Gjinovci A , et al. Dietary phytoestrogens activate AMP-activated protein kinase with improvement in lipid and glucose metabolism. Diabetes 2008; 57 (5) 1176-1185
- 22 Hurley RL, Barré LK, Wood SD , et al. Regulation of AMP-activated protein kinase by multisite phosphorylation in response to agents that elevate cellular cAMP. J Biol Chem 2006; 281 (48) 36662-36672
- 23 Bulun SE, Rosenthal IM, Brodie AM , et al. Use of tissue-specific promoters in the regulation of aromatase cytochrome P450 gene expression in human testicular and ovarian sex cord tumors, as well as in normal fetal and adult gonads. J Clin Endocrinol Metab 1993; 77 (6) 1616-1621
- 24 Jenne DE, Reimann H, Nezu J , et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet 1998; 18 (1) 38-43
- 25 Koo SH, Flechner L, Qi L , et al. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature 2005; 437 (7062) 1109-1111
- 26 Brown KA, McInnes KJ, Hunger NI, Oakhill JS, Steinberg GR, Simpson ER. The subcellular localization of CRTC2 provides a link between obesity and breast cancer in the postmenopausal woman. Cancer Res 2009; 69: 5392-5398
- 27 Subbaramaiah K, Morris PG, Zhou XK , et al. Increased levels of COX-2 and prostaglandin E2 contribute to elevated aromatase expression in inflamed breast tissue of obese women. Cancer Discov 2012; 2 (4) 356-365
- 28 Brown KA, Hunger NI, Docanto M, Simpson ER. Metformin inhibits aromatase expression in human breast adipose stromal cells via stimulation of AMPK. Breast Cancer Res Treat 2010; 123: 591-596