Cancer is not just a disease, but a dark phenomenon with social, emotional and economical implications that by now seems to have touched every single person on Earth. Each day brings more and more stories of people being affected and, unfortunately, statistics indicate a rising trend.
Early detection can significantly influence prognosis and this is one area Baylor College of Medicine researchers are looking to improve, using a novel approach. While there are many factors that can influence the development of cancer, a key mechanism is generally DNA damage. In most cases, this is the result of events that occur within cells and is mediated by cellular components, including proteins.
“Cancer is a disease of mutations. A normal cell that has accumulated several mutations in particular genes becomes likely to turn into a cancer cell”, noted corresponding author Dr. Susan M. Rosenberg.
In order to expose the DNA “damage-up” proteins in humans, the team looked at what would cause DNA damage in the bacterium E. coli when overproduced, a relatively frequent cellular event in both organisms. “Although bacteria and people are different, their basic biological processes are similar, so with this approach we thought we might find common mechanisms of DNA damage that could be relevant to cancer”, explained Rosenberg.
They genetically modified samples so that bacteria would light up red when DNA was deteriorated. Next, they overexpressed each of the 4,000 genes found in E-coli individually and determined which ones made bacteria glow red. 284 human protein relatives that could cause cancer were identified. Furthermore, the proteins’ RNAs, an indicator of protein production, predicted mutagenesis in tumors and poor patient outcomes.
The discovery could open up new therapeutic avenues and also possible novel mechanisms of protecting the genome. It also revealed new targets for current and future treatments.
“We showed that E. coli can help to identify DNA damage-up proteins and mechanisms of action in human cells quickly and inexpensively. Some of the proteins and their mechanisms were known to be involved in cancer, but many others were not suspected of being in the cancer-causing list”, added co-corresponding author Dr. Christophe Herman, professor of molecular and human genetics.
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