In a new finding that could lead to more effective and novel cancer treatments, scientists at the Albert Einstein College of Medicine report today that they have implicated a specific gene in the development of neuroblastoma. Although the research specifically deals with neuroblastoma, a lethal form of malignant tumor affecting children, the gene, called Id2, is also thought to be an important player in numerous other cancers. The study appears in the October 5, 2000, issue of the journal Nature.
The Einstein scientists found that neuroblastomas produce unusually high levels of Id2. The exorbitant amounts of Id2 undermine the function of one of the most important proteins responsible for prevention of tumor growth, the Retinoblastoma protein.
In neuroblastoma, accumulation of Id2 results from the activation of an important gene for cellular proliferation, the N-myc oncogene, which is present in multiple copies in this tumor. Although it was known that N-myc counteracts the function of the retinoblastoma protein, this study provides the missing link between activation of N-myc and nullification of tumor suppression by the Retinoblastoma protein.
"Understanding these details of cancer at the genetic level should enable us to find new weapons to fight the disease," says Dr. Antonio Iavarone, the Mark Trauner Faculty Scholar in Neuro-Oncology at Einstein who was co-leader of the study along with Dr. Anna Lasorella.
Iavarone and Lasorella have been exploring the role of Id2 for many years, during which time they became aware that Id2 has a crucial function in normal development: it triggers the production of brain cells. They hypothesized that as soon as the required number of cells has been generated during normal development, the Retinoblastoma protein shuts off Id2. To test their hypothesis, the researchers used mouse embryos genetically engineered to lack the Retinoblastoma protein. These mice die before birth because of the excessive growth of brain cells. But when the researchers also deleted Id2, the embryos lacking the Retinoblastoma protein survived their entire gestation and were born normally. In pathological conditions, on the other hand, Id2 eludes the barrier imposed by the retinoblastoma protein--the result is cancer.
"This study illustrates that certain pediatric cancers, such as neuroblastoma, originate from normal developmental processes gone awry," Dr. Lasorella says.
Id2 is thus the first gene shown both to submit to the control of its natural partner, the Retinoblastoma protein, during normal development and to cripple the tumor suppressor function of the same protein by accumulating in malignant tumors. "We can now develop drugs that will counteract the Id2 gene," says Iavarone. "Such drugs should provide a highly, targeted, effective treatment against neuroblastoma - and perhaps other cancers as well."
Journal
Nature