University of Kentucky researchers have created a cancer-resistant mouse by introducing a tumor-suppressor gene called 'Par-4' into an egg. The 'Par-4' gene, discovered in 1993, kills cancer cells, but not normal cells. It was originally found in the prostate, but this gene also can lead to the death of a broad range of cancer cells. In their new experiments, the scientists discovered that the 'Par-4' gene was transmitted to new generations of mice. The next step will to use this gene in humans through bone marrow transplantation, but there is still work to be done before that. Anyway, this sounds like good news for people affected with cancers.
This research project was led by Vivek Rangnekar, professor of radiation medicine at the University of Kentucky. You can see a picture of him on the left. He worked on this project with other researchers from the universities of Kentucky and Nebraska.
So what makes mice possessing this gene so interesting? "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."
The fact that there are no toxic side effects is a potential good news from all the people affected by a cancer. "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."
As Rangnekar said, "When a cancer patient goes to the clinic, they undergo chemotherapy or radiation and there are potential side effects associated with these treatments. 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."
And he added: "If you look at the pain that cancer patients go through, not just from the disease, but also from the treatment -- it's excruciating. If you have someone in your family, like I did, who has gone through that, you know you can see that pain. If you can not only treat the cancer, but also not harm the patient, that's a major breakthrough. That's happening with these animals and I think that's wonderful."
This research work has been published in Cancer Research under the name "Cancer Resistance in Transgenic Mice Expressing the SAC Module of Par-4" (Volume 67, Number 2, Pages 9276-9285, October 1, 2007). Here is a link to the abstract. "Prostate apoptosis response-4 (Par-4) is a tumor-suppressor protein that induces apoptosis in cancer cells, but not in normal/immortalized cells. The cancer-specific proapoptotic action of Par-4 is encoded in its centrally located SAC domain. We report here the characterization of a novel mouse model with ubiquitous expression of the SAC domain. Although SAC transgenic mice displayed normal development and life span, they were resistant to the growth of spontaneous, as well as oncogene-induced, autochthonous tumors. Resistance to tumorigenesis was linked to inhibition of nuclear factor-B activity and induction of apoptosis by the SAC domain. Collectively, our findings provide genetic evidence that the SAC domain of Par-4 confers cancer resistance in transgenic mice without compromising normal viability or aging, and may have therapeutic significance."
I hope that this research work will lead to less pain for people affected with cancers in the future.
Sources: University of Kentucky news release, November 27, 2007; and various websites
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