Key inflammatory marker is linked to cancer
Researchers at the University of Illinois at Urbana-Champaign have made interesting progress in the fight against cancer. The new study, that was published in the journal Oncogene, shows how an important component of the inflammatory response and immune cell growth can become an important factor in tumor growth. Jekyll-and-Hyde molecule NF-kappa B, as the researchers called it, is a first responder in immune and inflammatory response. Jekyll-and-Hyde molecule NF-kappa B is found in the cell cytoplasm and when bacteria and viruses enter the body this molecule activates gene transcription leading to inflammation and cell proliferation.
It was known for a long time that an overactive form of NF-kappa B is involved in signaling pathways in the nucleus but no one knew what keeps it active in the nucleus. University of Illinois Medical Biochemistry professor Lin-Feng Chen, noted that in healthy cells NF-kappa B is found in the cytoplasm, not the nucleus, and is inactive. But in cancer cells without any stimulation you can see this nuclear form of NF-kappa B. The cell just won’t die because of this. That is why NF-kappa B is so important in cancer, ” Chen said. He added that in order to activate NF-kappa B, normal cells must be stimulated. However, in cancer cells activation of this form nuclear NF-kappa B occurs without any stimulation, and this leads to cell proliferation.
Now, Chen and his team of researchers found that another molecule, called BRD4, which helps regulate gene expression, recognizes an acetylated amino acid of the a subunit of NF-kappa B protein complex. Only after that amino acid is acetylated, BRD4 can bind to NF-kappa B. This connection allows the activation of NF-kappa B and prevents its degradation in cancer cells. Researchers knew about this recognition, but what no one knew that this recognition has implications in cancer.
To see if BRD4 leads to sustained presence of NF-kappa B protein in the nucleus, the team of researchers led by Chen exposed lung cancer cells in cell culture and in immune-deficient mice to JQ1 (a drug that regulates the activity of BRD4). It was found that exposure to JQ1 interrupted the interaction between NF-kappa B. Thus the genes regulated by NF-kappa B were not expressed and proliferation of lung cancer cells decreased. In other words, researchers were able to suppress the ability of lung cancer cells to induce tumors in immune-deficient mice. Chen said that this study demonstrates that one day epigenetic regulators and NF-kappa B can be targets for cancer therapy.