Activation of two related proteins with a small molecule, exert a lethal blow against glioblastoma cells, report researchers from Georgetown Lombardi Comprehensive Cancer Center.
The scientists say when activated, one protein, called the short form, stops glioblastoma cells from replicating their DNA, and the other, called the long form, prevents cell division if the DNA has already been replicated, explains Rebecca Riggins, PhD, assistant professor of oncology at Georgetown Lombardi. Both proteins are produced by the estrogen-related receptor beta (ERR) gene. They are known as "orphan receptors" as they don't bind to any substances naturally produced by the body.
ERR proteins are similar in shape to the receptor that binds the hormone estrogen and hence their name. But they do not bind estrogen and are not otherwise related. Both men and women have ERR genes. In this study, Riggins and Mary Heckler, PhD, examined glioblastoma cells in the laboratory for the presence of ERR and found both long and short forms. They used a laboratory chemical, DY131, to study the action of the enzyme which had been designed to bind and activate these proteins.
The researchers discovered that DY131 exerted a strong, but distinct, effect on both the short and long forms of ERR. The short form had been known to act as a tumor suppressor in prostate cancer, and a similar anti-cancer action was found by the researchers in glioblastoma. The study, however, is the first to find a function for the long form in cancer. "While much work remains to understand the clinical potential of this finding, it may ultimately be possible to directly target the long and short forms of ERR in combination with other therapies to improve outcomes in glioblastoma," Riggins says.