Friday, December 7, 2007
Cancer-resistant Mouse is Created
A mouse resistant to cancer, even highly-aggressive types, has been created by researchers at the University of Kentucky. The breakthrough stems from a discovery by UK College of Medicine professor of radiation medicine Vivek Rangnekar and a team of researchers who found a tumor-suppressor gene called "Par-4" in the prostate. The researchers discovered that the Par-4 gene kills cancer cells, but not normal cells. There are very few molecules that specifically fight against cancer cells, giving it a potentially therapeutic application. Rangnekar's study is unique in that mice born with this gene are not developing tumors. The mice grow normally and have no defects. In fact, the mice possessing Par-4 actually live a few months longer than the control animals, indicating that they have no toxic side effects.
"We originally discovered Par-4 in the prostate, but it's not limited to the prostate. The gene is expressed in every cell type that we've looked at and it induces the death of a broad range of cancer cells, including of course, cancer cells in the prostate," said Rangnekar. The gene helps cells self-destruct when they become cancerous. The modified mice -- which came from a strain that's normally vulnerable to the disease -- resisted researchers' attempts to give them breast, pancreatic, head and neck cancer. "The interesting part of this study is that this killer gene is selective for killing cancer cells. It will not kill normal cells and there are very, very few selective molecules out there like this." To further investigate the potential therapeutic benefits of this gene, researchers introduced it into the egg of a mouse. That egg was then planted into a surrogate mother. "The mouse itself does not express a large number of copies of this gene, but the pups do and then their pups start expressing the gene," Rangnekar said. "So, we've been able to transfer this activity to generations in the mouse."
The implications for humans could be that through bone marrow transplantation, the Par-4 molecule could potentially be used to fight cancer cells in patients without the toxic and damaging side effects of chemotherapy and radiation therapy. "When a cancer patient goes to the clinic, they undergo chemotherapy or radiation and there are potential side effects associated with these treatments," Rangnekar said. "We got interested in looking for a molecule which will kill cancer cells and not kill normal cells, but also would not be toxic with regard to the production of side effects to the entire organism. We are thinking of this in a holistic approach that not only would get rid of the tumor, but also not harm the organism as a whole. Before this animal study, we published a lot of work indicating that in cell culture, there's no killing of normal cells. This is the proof that it doesn't kill normal cells because the mouse is alive and healthy."
In the short term, bone marrow transplants of Par-4 producing cells could be tested as an alternative to risky chemical and radiation therapies in people. Those approaches destroy both healthy and diseased tissue, while Par-4's protein affects only cancer cells. Rangnekar admits there is much more work to be done before this research can be applied to humans, but agrees that is the most logical next step.
Image: courtesy of corbis, www.corbis.com