Researchers identify gene that regulates tumors in neuroblastoma

According to Paul B. Fisher, M.Ph., Ph.D., who is the first incumbent of the Thelma Newmeyer Corman Endowed Chair in Cancer Research with the VCU Massey Cancer Center, and Seok-Geun Lee, Ph.D., assistant professor in the VCU Department of Human and Molecular Genetics, co-lead investigators of the study, the team has shown that astrocyte elevated gene-1, AEG-1, a cancer promoting gene, is frequently activated in neuroblastoma.

In the study published online in the May issue of the journal Oncogene, Fisher, Lee and their team found that the elevated expression of AEG-1 makes cancer cells highly aggressive and resistant to factors that may influence cell suicide, and that loss of AEG-1 reduces the tumor-causing 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.

Furthermore, they have shown the potential correlation between AEG-1 and MYCN in neuroblastoma. MYCN is a known genetic determinant of neuroblastoma and elevated levels have been observed in one third of neuroblastoma patients. MYCN is linked 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. This works shows that AEG-1 plays a crucial role in the development and progression of neuroblastoma through activating important signaling pathway and induction of MYCN,” said Fisher, who also is professor and chair of the Department of Human and Molecular Genetics, and director of the VCU Institute of Molecular Medicine in the VCU School of Medicine.

“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,” he said.

The team has already begun analyzing the expression of AEG-1 and its relationship with MYCN status in neuroblastoma patient samples. Through collaboration with John Maris, M.D., chair of neuroblastoma research at the University of Pennsylvania School of Medicine, the team will acquire data from approximately 2,000 neuroblastoma patient tissues. They will also test if inactivation of AEG-1 using small interfering RNA could be a therapeutic intervention for neuroblastoma through second collaborative effort with Bill Weiss, M.D., associate professor of Neurology at the University of California, San Francisco.

This work was supported by grants from the National Institutes of Health, the Samuel Waxman Cancer Research Foundation, the Dana Foundation, and the Goldhirsh Foundation.

Fisher worked with a team that included VCU School of Medicine researchers Zaozhong Su, Ph.D., associate professor in the VCU Department of Human and Molecular Genetics; Devanand Sarkar, M.B.B.S., Ph.D., assistant professor and Harrison Endowed Scholar in Cancer Research at the VCU Massey Cancer Center, the VCU Institute of Molecular Medicine and the Department of Human and Molecular Genetics; H-Y Jeon, J.E. Richards, and N. Vozhilla, D.V.M., with the VCU Department of Human and Molecular Genetics; and T Van Maerken, M.D., with the Center for Medical Genetics at the Ghent University Hospital in Ghent, Belgium.

EDITOR’S NOTE: A copy of the study is available for reporters by email request from j.john@natureny.com.

About VCU and the VCU Medical Center:

Virginia Commonwealth University is the largest university in Virginia with national and international rankings in sponsored research. Located on two downtown campuses in Richmond, VCU enrolls 32,000 students in 205 certificate and degree programs in the arts, sciences and humanities. Sixty-five of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 15 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University compose the VCU Medical Center, one of the nation’s leading academic medical centers. For more, see www.vcu.edu.

About the VCU Massey Cancer Center:

The VCU Massey CancerCenter is one of 63 National Cancer Institute-designated institutions that leads and shapes America’s cancer research efforts. Working with all kinds of cancers, the Center conducts basic, translational and clinical cancer research, provides state-of-the-art treatments and promotes cancer prevention and education. Since 1974, Massey has served as an internationally recognized center of excellence. It offers more clinical trials than any other institution in Virginia, serving patients in Richmond and in four satellite locations. Treating all kinds of cancers, its 1,000 researchers, clinicians and staff members are dedicated to improving the quality of human life by developing and delivering effective means to prevent, control and, ultimately, to cure cancer. Visit Massey online at www.massey.vcu.edu or call 1-877-4-MASSEY.