The scientists began their study attempting to confirm previous work, including their own, suggesting that Id1 activation was an important step in tumor angiogenesis, a process that builds blood vessels needed for tumor growth.
In the earlier research on Id1, scientists used a mouse model in which tumor cells were injected directly into the animals to stimulate cancer growth: in effect, a tumor transplant. The tumors grew in the animals with Id1 activation while the injected tumors failed to grow in mice whose Id1 genes were inactivated.
"But this is not how people get cancer," says Rhoda Alani, M.D., director of the study and assistant professor of oncology, dermatology, molecular biology and genetics at the Johns Hopkins Kimmel Cancer Center. "We get cancer through a series of genetic events that occur over time, triggered by both internal and external factors."
In the Hopkins investigator's new model, mice were exposed to carcinogens placed on their skin and allowed to gradually develop cancer. Results showed a completely opposite outcome with respect to Id1: all mice with the Id1 gene turned off developed more tumors that also were larger than in previous studies.
"Clues to promising cancer drug development are only as good as the model in which you study a process," says Alani. "If knocking out the Id1 gene in two different models produces two different results, then we need to reevaluate the role that Id1 plays in angiogenesis."