Huebner and colleagues at Ohio State and Thomas Jefferson University bred two strains of mice, one that had only one copy of the FHIT gene, and another that lacked both copies. They also established a control group of normal mice that had both copies of the gene.
They exposed all the mice to NNK, a powerful carcinogen commonly found in tobacco smoke that researchers believe plays a major role in human lung cancer.
They discovered that while mice deficient in the FHIT gene's protein did not develop lung tumors any more frequently than did normal mice, the tumors they did develop were larger and more numerous. In addition, the severity of the tumor growth appeared to follow a continuum paralleling the loss of the protein. While the normal mice developed only benign tumors, 17 percent of the mice that had lost one copy of the gene developed malignant tumors and all of the tumors in the mice that lost both copies of the gene were malignant.
"This suggests that even very low levels of the protein might be enough to suppress or even prevent lung cancer," says Huebner.
Huebner had a hunch that pairing loss of protein with the loss of another tumor suppressor might enhance the research value of the new mouse model even more, so the research team bred another strain of mice that coupled the lack of the protein with partial loss of a second tumor suppressor gene, VHL, which also sits on chromosome 3 in humans. (Mice with loss of both copies of VHL do not survive.)
"We chose this gene because VHL is important in regulating angiogenesis, or the growth of blood vessels that tumors need to support themselves," says Huebner. "When VHL is in place and working properly, it blocks angiogenesis."
Interestingly, humans whose VHL gene is lost or mutated suffer from a condition called Von-Hippel Lindau disease, an inherited disorder characterized by abnormal blood vessel growth in the eyes, brain, sp
Source:Ohio State University