RICHMOND, Va.—
Virginia Commonwealth University (VCU) researchers recently announced they have identified a gene that may play a key role in regulating tumor progression in neuroblastoma, a form of cancer usually found in young children. This particular culprit—and potential lead on developing a therapy to inhibit the expression of this gene—turns out to astrocyte elevated gene-1 (AEG-1).
According to Dr. Paul B. Fisher and Dr. Seok-Geun Lee, co-lead investigators of the study, the team has shown that AEG-1, a cancer promoting gene, is frequently activated in neuroblastoma. Fisher is the first incumbent of the Thelma Newmeyer Corman Endowed Chair in Cancer Research with the
VCU Massey Cancer Center, and Lee is an assistant professor in the
VCU Department of Human and Molecular Genetics.
In the study, published online in the May issue of the Nature Publishing Group journal
Oncogene, the team reported that the elevated expression of AEG-1 makes cancer cells highly aggressive and resistant to factors that may influence cell suicide. Moreover, knockdown of AEG-1 by small interfering RNA reduced the tumorigenic properties of highly aggressive neuroblastoma cells. Additionally, the expression of AEG-1 was significantly elevated in six of 10 neuroblastoma patient-derived samples compared to normal peripheral nerve tissues.
They also report a potential correlation between AEG-1 and the MYCN gene in neuroblastoma. MYCN is a known genetic determinant of neuroblastoma, with elevated levels have been observed in one third of neuroblastoma patients, and MYCN is linked both to aggressive tumor formation and poor clinical outcome.
"We believe that activation of AEG-1 in addition to MYCN is critical to the development and progression of neuroblastoma," Fisher says. "This work shows that AEG-1 plays a crucial role in the development and progression of neuroblastoma through activating important signaling pathway and induction of MYCN. In addition, we have shown that AEG-1 could be a potential prognostic marker for neuroblastoma and a potential target for novel therapeutic strategies for neuroblastoma patients."
The VCU researchers have already begun analyzing the expression of AEG-1 and its relationship with MYCN status in neuroblastoma patient samples, and the team will acquire data from approximately 2,000 neuroblastoma patient tissues through a collaboration with Dr. John Maris, chair of neuroblastoma research at the
University of Pennsylvania School of Medicine. Through a second collaborative effort with Dr. Bill Weiss, associate professor of neurology at the
University of California, San Francisco, they will also test if inactivation of AEG-1 using small interfering RNA could be a therapeutic intervention for neuroblastoma.
In the United States, some 650 children are diagnosed with neuroblastoma each year. Often, the disease is present at birth but is not detected until the tumor begins to grow and compress the surrounding organs.
Although the sheer number of annual cases may not be large, the VCU discoveries with regard to neuroblastoma are important, Fisher notes, because the disease is the most common extracranial solid tumor of childhood.
According to information from VCU, most children affected by neuroblastoma have been diagnosed before the age of 5, and it is the most common tumor found in children younger than 1 year of age. Experts have estimated that as many as 20 percent of neuroblastoma cases result from an inherited mutation, followed by a second mutation occurring after birth, which together initiate uncontrolled cell growth. The remaining cases occur from two acquired mutations after birth. Because the tumor occurs very early in childhood, it is considered unlikely that a child's environmental exposures would be linked to the development neuroblastoma.
The work leading to the study published in
Oncogene was supported by grants from the
National Institutes of Health, the
Samuel Waxman Cancer Research Foundation, the
Dana Foundation, and the
Goldhirsh Foundation.
