Researchers at UT Southwestern Medical Center have found a biological indicator that may help identify which glioblastoma patients have the most aggressive forms of the disease. Additionally, they found that this molecule, RIP1, negatively regulates p53.
Reporting in the April issue of Cancer Research, the scientists found RIP1 (receptor interacting protein 1) in high levels in glioblastoma. RIP1 is a component of the complex NF-kB signaling network, a family of proteins that play a key role in inflammation-induced cancer. They note that this is the first time that high RIP1 levels have been associated with any type of cancer.
The team observed that RIP1 is commonly overexpressed in glioblastoma but not in grades II and III glioma. Additionally, increased expression of RIP1 confered a worse prognosis.
RIP1 also levels correlated strongly with mdm2 levels in glioblastoma. “RIP1 activates NF-kB and then that increases the expression of a gene called mdm2, which inhibits the p53 gene,” explains Amyn Habib, M.D., assistant professor of neurology at UT Southwestern. “Inhibition of p53 allows cells with damaged DNA to proliferate and potentially to become cancerous.”
In the study titled “The Receptor Interacting Protein 1 Inhibits p53 Induction through NF-B Activation and Confers a Worse Prognosis in Glioblastoma,” researchers examined tumor tissues from 92 patients to determine the distribution of RIP1 in each. One of the next steps is to determine whether these patients may respond better to drugs targeting the NF-kB network.