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Exploring the Proteomic and Genomic Relationships between CtBP Expression and Metabolic Imbalance in Breast Cancer
Author(s) -
Crawford Lindsey,
HernandezMora Roberto,
Park Sam,
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.698.13
Subject(s) - breast cancer , cancer , medicine , disease , body mass index , obesity , oncology , mortality rate , incidence (geometry) , endocrinology , cancer research , physics , optics
Over 200,000 American women are diagnosed with breast cancer annually. Although the mortality rate of diagnosed patients has decreased over the years, there are still breast cancer health disparities that exist in the United States. Research studies have shown that although European American women have the highest breast cancer incidence rate, the highest breast cancer death rate is observed in African American women. Additionally, obesity has also been associated with an increased risk of breast cancer in postmenopausal women, having a three times higher risk of death from disease, with a body mass index (BMI) greater than 40 kg/m 2 , compared to their healthier counterparts. Our lab is currently focused on analyzing the role of C‐Terminal Binding Proteins (CtBP), a family of NADH‐dependent nuclear regulators that respond to metabolic imbalance and function as transcriptional corepressors when targeted to gene promotors. As cancer cells exhibit higher levels of lactic acid production and glucose consumption in the presence of a significant amount of oxygen, the steady state levels of NADH rises creating aNAD+/NADH redox imbalance. This metabolic imbalance, called the Warburg Effect, can be linked to CtBP's possible role in breast cancer. Using Immunohistochemistry and RNA‐seq to profile both the protein levels and RNA expression, we are exploring the trends across the breast cancer subtypes and determining how they correlate with certain patient parameters, such as ethnicity, menopausal status, ERstatus, and BMI. From the numerous fixed parameters, multiple correlations within the patient data set were found revealing an intriguing set of trends that form the basis for future analysis. For example, we have discovered a correlation between high protein levels of CtBP with the Luminal B subtype, a more aggressive subtype of estrogen receptor positive breast cancer. Although a high gene expression of ESPL1, a newly discovered Luminal B breast cancer subtype oncogene, has also been correlated with Luminal B, ESPL1 was anti‐correlated with CtBP. This finding suggests that there may be two different molecular/phenotypic subtypes of Luminal B. The significant anti‐correlation between ESPL1 and CtBP was not seen in the other breast cancer subtypes. Notably this relationship is significantly modified by Race, menopausal status and BMI. The trends found exploring the proteomic and genomic relationships allows us to begin to explore how CtBP may link race and metabolic status with gene expression and outcome in breast cancer.