CHAPEL HILL,NC -- Scientists at the University of North Carolina at Chapel Hill have found that a gene discovered earlier in the decade has paradoxical properties -- it helps bring about tumor cell death yet is also necessary for their growth. The new study highlights an important molecular mechanism in the evolution of tumors and could lead to new anti-cancer drugs targeted to a specific gene.
A report published in the Sept. 24 issue of Molecular Cell focuses on the gene E2F1, a cell cycle regulating molecule first identified in 1992. On the molecular chain of events leading to tumor formation and growth, E2F1 exerts its action "upstream" of the tumor suppressor gene known to researchers as p53, according to the new study.
Study senior author Dr. Terry Van Dyke, professor of biochemistry and biophysics at UNC-CH School of Medicine, says E2F1 apparently prompts p53 to defend against developing tumors: apoptosis ? programmed cell death. The study examined mice that had been genetically engineered in Van Dyke?s laboratory to develop a type of cancerous brain tumor that occurs rarely in people. Some of these "transgenic" mice were selectively bred not to have E2F1.
"We found that cell death was diminished by 80 percent in the tumors of animals without E2F1," Van Dyke says.
But the researcher and her colleagues also discovered that without E2F1 the growth of brain tumors slowed considerably, even though the rate of tumor cell death had dropped sharply.
"This was surprising. Although p53 cell death drops because E2F1 is not there to induce it, tumor growth does not accelerate," Van Dyke says. "And the reason the growth rate is not accelerated, we discovered, is that E2F1 is required also for proliferation of the tumor cells."
Thus E2F1 is a kind of molecular paradox. Not only does it help suppress tumors,
its presence is also needed for tumor growth. Moreover, unlike p53, which is
absent in about half of cancers, E2F1is not deleted from
Contact: Leslie Lang
University of North Carolina School of Medicine