Instead, the idea is to indirectly attack the tumors by creating a genetically restrictive environment. If neurofibromatosis patients dont develop the benign tumors, they cant develop cancer from them, Parada said.
Every cell in the body carries a complete copy of the genetic code that controls human development. Included in that code are tumor suppressors whose function is to control unrestricted cell growth. People normally have two NF-1 copies (alleles), one contributed from each parents genetic structure. NF-1 patients are born with one allele missing. The researchers discovered that when the one normal allele disappears from a particular type of cell, known as a Schwann cell, the cell can mutate and spawn a benign tumor.
In trying to develop a mouse model that replicated human NF-1, Zhu and his colleagues found that mice born with only one normal allele never develop the disorder because the odds are in their favor - they dont live as long as humans and dont have as many cells that could lose the one good allele and form tumors; however, mouse models with both alleles missing died before birth.
The researchers then genetically engineered two kinds of mice one type with only one allele and one type with two alleles. In both, they nullified the alleles specifically in Schwann cells. But not all of the mice developed NF-1. The disease surfaced only in mice whose non-Schwann cells carried only one normal NF-1 allele. Mice that carried two normal alleles in all other cells didnt develop tumors.
This model system demonstrates that for this type of tumor, there are two environments, Parada said. That immediately opens the notion that it might also be true for many types of cancers.
But the focus remains on neurofibromatosis. Parada said the latest research is dedicated in memory of Elisabeth Reed Wagner, who passed away April 11, 12 days shy of her 21st birthday. She had battled NF-1 since age 3 and had b
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Contact: Wayne Carter
Wayne.Carter@UTSouthwestern.edu
214-648-3404
UT Southwestern Medical Center
2-May-2002