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NIH: Molecular link found between metabolism, breast cancer
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Researchers from the National Cancer Institute have identified a protein linked to diabetes and obesity that could be a factor in the development of aggressive forms of breast cancer, according to a press release from the US Department of Health and Human Services. The findings were published in Nature Communications.
Previous research has shown that C-terminal binding proteins (CtBP1/2) repressed the transcriptional expression of the BRCA1gene, the researchers wrote.
“Modifying diet and maintaining a healthy diet, combined with developing pharmacological ways of lessening CtBP activity, may one day lead to a way to break the link between cancer and obesity,” study researcher Kevin Gardner, MD, PhD, head of NCI’s Transcription Regulation Section, Genetics Branch, said in a press release.
The repression prompted researchers to profile the global association of CtBP with the genome of breast cancer cells by combining chromatin immunoprecipitation with deep sequencing (ChIP-Seq) to identify cellular programs induced by the protein, they wrote.
This expansion of research included analyzing prior gene expression studies to observe whether gene pathways repressed by CtBP declined in patients with breast cancer who experienced aggressive clinical outcomes. They measured the link between CtBP and the genes it bound to with the human breast cancer cells. Combining this concept with genome sequencing, they sought to determine how and where CtBP played a role in breast cancer development. Finally, they inhibited gene expression through the reduction of carbohydrates.
Data indicate an increased repair of DNA, causing stability and growth control in cases in which researchers reduced levels of CtBP. However, gene pathways targeted by CtBP appeared to be agitated in more aggressive breast cancers, according to the press release.
Furthermore, the researchers discovered that patients with high levels of CtBP in their tumors also had a shorter survival rate; and where reduction of carbohydrates was conducted, researchers concluded that gene-repression was able to be reversed.
“Our new work suggests that targeting CtBP may provide a way of treating breast cancer and possibly preventing breast cancer,” Gardner said in the release. “Research should continue to focus on the link between obesity, CtBP and breast cancer. This will require more population-based studies and multidisciplinary teams of scientists to investigate these links.”
Disclosure: One of the researchers is an equity stock holder of BioClassifier LLC and University Genomics; and also filed a patent on the PAM50 assay (gene expression profiles to predict breast cancer outcomes, US Patent Application 20110145176).
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