Researchers from IDIBELL have collaborated on a study characterizes a protein called RBM38, key in the regulation of tumor cell death, which is disabled in breast tumors, making them more resistant to some chemotherapy treatments.
The p53 protein known as guardian of the genome is responsible for removing premalignant cells. Researchers have found that RBM38 helps this defense by controlling small regulatory molecules called microRNAs. The IDIBELL researcher, Manel Esteller, has explained that “this normal function of RBM38 that would remove the cells with defects which may cause a tumor is lost in breast cancer.”
The study concludes that breast tumors epigenetically inactivate the RBM38 gene (there is a chemical alteration in the DNA of the gene coding for this protein) so that it cannot interact with p53 and microRNAs to prevent abnormal growth. “It would be as a failed peace UN mission” explained Esteller.
According to Manel Esteller, this finding not only will deepen the understanding of the origins of cancer, but it may also have a practical application. “Breast tumors in which RBM38 protein doesn’t work are particularly ressistent to certain chemotherapies, such as those containing doxorubicin. So it could help select for these patients, treatments with other drugs to maximize the likelihood that patients respond to therapy.
Nicolas Léveillé, Ran Elkon, Veronica Davalos*, Vijayalaxmi Manoharan, Dave Hollingworth, Joachim Oude Vrielink, Carlos le Sage, Carlos A. Melo, Hugo M. Horlings, Jelle Wesseling, Jernej Ule, Manel Esteller*, Andres Ramos & Reuven Agami.Selective inhibition of microRNA accessibility by RBM38 is required for p53 activity. Nature Communications 2:513. doi: 10.1038/ncomms1519