scholarly journals Paracrine-Acting Adiponectin Promotes Mammary Epithelial Differentiation and Synergizes with Genistein to Enhance Transcriptional Response to Estrogen Receptor β Signaling

Endocrinology ◽  
2011 ◽  
Vol 152 (9) ◽  
pp. 3409-3421 ◽  
Author(s):  
Omar M. Rahal ◽  
Rosalia C. M. Simmen
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Soy Protein Isolate ◽  
Dietary Exposure ◽  
Dietary Factors ◽  
Mammary Epithelial ◽  
Mammary Tissue

Mammary stromal adipocytes constitute an active site for the synthesis of the adipokine, adiponectin (APN) that may influence the mammary epithelial microenvironment. The relationship between “local,” mammary tissue-derived APN and breast cancer risk is poorly understood. Here, we identify a novel mechanism of APN-mediated signaling that influences mammary epithelial cell proliferation, differentiation, and apoptosis to modify breast cancer risk. We demonstrate that early dietary exposure to soy protein isolate induced mammary tissue APN production without corresponding effects on systemic APN levels. In estrogen receptor (ER)-negative MCF-10A cells, recombinant APN promoted lobuloalveolar differentiation by inhibiting oncogenic signal transducer and activator of transcription 3 activity. In ER-positive HC11 cells, recombinant APN increased ERβ expression, inhibited cell proliferation, and induced apoptosis. Using the estrogen-responsive 4X-estrogen response element promoter-reporter construct to assess ER transactivation and small interfering RNA targeting of ERα and ERβ, we show that APN synergized with the soy phytoestrogen genistein to promote ERβ signaling in the presence of estrogen (17β-estradiol) and ERβ-specific agonist 2,3-bis(4-hydroxyphenyl)-propionitrile and to oppose ERα signaling in the presence of the ERα-specific agonist 4,4′,4′-(4-propyl-(1H)-pyrazole-1,3,5-triyl)trisphenol. The enhancement of ERβ signaling with APN + genistein cotreatments was associated with induction of apoptosis, increased expression of proapoptotic/prodifferentiation genes (Bad, p53, and Pten), and decreased antiapoptotic (Bcl2 and survivin) transcript levels. Our results suggest that mammary-derived APN can influence adjacent epithelial function by ER-dependent and ER-independent mechanisms that are consistent with reduction of breast cancer risk and suggest local APN induction by dietary factors as a targeted approach for promotion of breast health.

scholarly journals Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis

2018 ◽  
Vol 48 (3) ◽  
pp. 795-806 ◽  
Author(s):  
Xiang Shu ◽  
Lang Wu ◽  
Nikhil K Khankari ◽  
Xiao-Ou Shu ◽  
Thomas J Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Type 2 Diabetes ◽  
Estrogen Receptor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Mendelian Randomization ◽  
Menopausal Status ◽  
Inverse Association ◽  
Fasting Insulin

Abstract Background In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p  =  5.09  ×  10–4], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p  =  4.02  ×  10–4), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p  =  5.05  ×  10–19) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p  =  9.22  ×  10–6). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2-h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.

scholarly journals Body mass index, mammographic density, and breast cancer risk by estrogen receptor subtype

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Yiwey Shieh ◽  
Christopher G. Scott ◽  
Matthew R. Jensen ◽  
Aaron D. Norman ◽  
Kimberly A. Bertrand ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Estrogen Receptor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Body Mass ◽  
Mammographic Density ◽  
Receptor Subtype

scholarly journals Logistic LASSO Regression for Dietary Intakes and Breast Cancer

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2652
Author(s):  
Archana J. McEligot ◽  
Valerie Poynor ◽  
Rishabh Sharma ◽  
Anand Panangadan
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Vitamin B12 ◽  
Dietary Factors ◽  
Dietary Intakes ◽  
Lasso Regression ◽  
Cancer Risk Factors ◽  
Breast Cancer Risk Factors

A multitude of dietary factors from dietary fat to macro and micronutrients intakes have been associated with breast cancer, yet data are still equivocal. Therefore, utilizing data from the large, multi-year, cross-sectional National Health and Nutrition Examination Survey (NHANES), we applied a novel, modern statistical shrinkage technique, logistic least absolute shrinkage and selection operator (LASSO) regression, to examine the association between dietary intakes in women, ≥50 years, with self-reported breast cancer (n = 286) compared with women without self-reported breast cancer (1144) from the 1999–2010 NHANES cycle. Logistic LASSO regression was used to examine the relationship between twenty-nine variables, including dietary variables from food, as well as well-established/known breast cancer risk factors, and to subsequently identify the most relevant variables associated with self-reported breast cancer. We observed that as the penalty factor (λ) increased in the logistic LASSO regression, well-established breast cancer risk factors, including age (β = 0.83) and parity (β = −0.05) remained in the model. For dietary macro and micronutrient intakes, only vitamin B12 (β = 0.07) was positively associated with self-reported breast cancer. Caffeine (β = −0.01) and alcohol (β = 0.03) use also continued to remain in the model. These data suggest that a diet high in vitamin B12, as well as alcohol use may be associated with self-reported breast cancer. Nonetheless, additional prospective studies should apply more recent statistical techniques to dietary data and cancer outcomes to replicate and confirm the present findings.

The Estrogen Receptor α Gene and Breast Cancer Risk (The Netherlands)

2005 ◽  
Vol 16 (10) ◽  
pp. 1195-1202 ◽  
Author(s):  
N. Charlotte Onland-Moret ◽  
Carla H. van Gils ◽  
Mark Roest ◽  
Diederick E. Grobbee ◽  
Petra H. M. Peeters
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
The Netherlands ◽  
Estrogen Receptor Α ◽  
Estrogen Receptor Α Gene

scholarly journals Interaction between dietary acrylamide intake and genetic variants for estrogen receptor-positive breast cancer risk

2018 ◽  
Vol 58 (3) ◽  
pp. 1033-1045 ◽  
Author(s):  
Janneke G. F. Hogervorst ◽  
Piet A. van den Brandt ◽  
Roger W. L. Godschalk ◽  
Frederik-Jan van Schooten ◽  
Leo J. Schouten
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Genetic Variants ◽  
Estrogen Receptor Positive ◽  
Dietary Acrylamide ◽  
Positive Breast Cancer

scholarly journals Obesity, Dietary Factors, Nutrition, and Breast Cancer Risk

2018 ◽  
Vol 10 (1) ◽  
pp. 14-27 ◽  
Author(s):  
Annina Seiler ◽  
Michelle A. Chen ◽  
Ryan L. Brown ◽  
Christopher P. Fagundes
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Dietary Factors
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