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Exploring Molecular and Morphological Relationships between Obesity and CtBP in Breast Cancer
Author(s) -
Park Sam Sangil,
Yi Dae Ik,
Li Daniel,
Crawford Lindsey,
Liang Genqing,
Kabbout Mohamed,
Hernandez Roberto,
Yan Tingfen,
Ambs Stefan,
Byun Jung S.,
Gardner Kevin
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.515.9
Subject(s) - breast cancer , epigenetics , epithelial–mesenchymal transition , cancer research , adipocyte , cancer , overweight , hormone , biology , medicine , metastasis , obesity , endocrinology , adipose tissue , gene , genetics
In the United States, 69% of adults are overweight or obese. This epidemic is associated with grave consequences, including increased breast cancer morbidity and mortality. One possible mechanism accounting for this elevated risk is adipocyte hypertrophy, which induces hormonal and immune dysregulations that may contribute to abnormal growth of surrounding epithelial cells. In addition, several metabolic intermediates associated with high carbohydrate food intake may influence cellular gene expression. One of these intermediates is NADH, which is elevated under conditions of obesity, diabetes, and metabolic syndrome. NADH stabilizes and activates C‐terminal binding protein (CtBP), a nuclear protein that plays a substantial epigenetic role in modifying gene expression. In particular, CtBP drives Epithelial‐Mesenchymal Transition, genome instability, and stem cell like pathways to induce tumor invasion and metastasis. In this study, we explore a link between obesity and CtBP by examining cohorts of breast cancer patient samples and in vitro assays. Using digital analysis of histological sections and immunohistochemistry, we correlate patient median adipocyte cross‐sectional area and BMI, along with gene and protein expressions of CtBP and its regulatory targets. These characteristics are then assessed in combination with patient parameters including age, race/ethnicity, and hormone receptor status. Furthermore, we perform functional in vitro assays by manipulating the levels of CtBP and glucose in human breast mammary cell lines. The goal of this study is to begin to understand how aspects of lifestyle and personal traits interact with the molecular pathways of CtBP to influence breast cancer incidence and mortality.