Genes Cause Cancer in Mice With Brain Tumors
CancerWise - September 2007
A gene found at the scene of a variety of tumors connects with other proteins to help cause and speed the growth of two types of treatment-resistant brain cancer, according to a recent study in mice.
Significance of results
The study, which was published in the Proceedings of the National Academy of Sciences, showed that insulin-like growth factor binding protein 2 (IGFBP2) plays an active role in the creation of astrocytoma and progression of oligodendroglioma, both forms of glioma.
Gliomas are brain tumors that develop in the glial cells. They are highly resistant to treatment.
"This makes IGFBP2 an important candidate for developing a targeted therapy," says senior author Wei Zhang, Ph.D., a professor in M. D. Anderson's Department of Pathology.
Cancer-causing proteins K-Ras and Akt and platelet-derived growth factor beta (PDGFB) were used in the study.
Scientists combined IGFBP2 with:
- K-Ras and Akt in mice in forming astrocytomas
- PDGFB in mice in forming oligodendrogliomas
The study reported these results involving:
- Mice with astrocytoma:
- IGFBP2 and K-Ras caused astrocytoma
- K-Ras and Akt caused astrocytoma
- Akt and IGFBP2 did not cause tumors
- Akt fuels cell growth and survival
- None of the genes alone caused cancer
- Mice with oligodendroglioma:
- IGFBP2 and PDGFB caused advanced cancer
- IGFBP2 and PDGFB activated the Akt pathway
- PDGFB alone does not activate the Akt pathway
In addition, researchers treated IGFBP2-PDGFB infected cells with a known Akt inhibitor. This killed more of the combination cells than those infected only with PDGFB.
The connection to Akt makes the presence of IGFBP2 in blood serum a potential biomarker. It might indicate an active role for Akt in a patient's cancer and thus a role for Akt inhibitors in the patient's treatment.
Zhang and fellow study leader Gregory Fuller, M.D., Ph.D., a professor in the Department of Pathology and chief of the Section of Neuropathology, first associated the overproduction of IGFBP2 with brain cancer in 1999.
Other researchers have since found it to be overproduced in prostate, ovarian, breast and colorectal cancers, some leukemias and other drug-resistant tumors.
"The rate of survival of patients with gliobastoma, the most advanced type of glioma, has not significantly improved for decades," Zhang says. "We hope IGFBP2 will provide an effective target for treatment of this devastating disease."
Because IGFBP2 is overproduced in several types of cancer, the possibilities are not limited to brain tumors, Zhang and Fuller say.
– From staff reports