Refusal of suicide order: Why tumor cells become resistantJune 24, 2008Cells with irreparable DNA damage normally induce programmed cell death, or apoptosis. However, this mechanism often fails in tumor cells so that transformed cells are able to multiply and spread throughout the body. Scientists at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have now discovered a possible cause of this failure. Tumor cells simply degrade a protein that triggers apoptosis in the case of DNA damage. Blocking this protein degradation might set apoptosis back in operation and, thus, increase the effectiveness of radiotherapy or chemotherapy. The researchers have now published their results in Nature Cell Biology. Proteins that trigger programmed cell death, or apoptosis, must be kept under careful control. After all, a cell should induce its own death only if its genetic material is damaged so severely that there is a danger of its transformation into a malignantly growing tumor cell. However, minor damages in the DNA can be corrected by the cell's special repair mechanisms - hence, no reason to commit suicide! Among the proteins that trigger apoptosis after severe DNA damage is the HIPK2 molecule. Scientists in Dr. Thomas Hofmann's research group at the German Cancer Research Center (DKFZ) have now shown that although HIPK2 is continuously produced in healthy cells, it is instantly degraded again. An enzyme called Siah-1 attaches labels to HIPK2 marking it as "garbage". Thus, the cell prevents that apoptosis is induced "accidentally".
Slightly damaged cells enter a kind of alarm status: They block degradation of HIPK2 by Siah-1 for a short time. But as soon as the damage is repaired, the cell immediately resumes labeling HIPK2 as garbage and degrades the molecule. Only in severely damaged cells, such as by a broken DNA double strand, degradation of HIPK2 by the Siah-1 enzyme is blocked permanently. As a result, HIPK2 accumulates, apoptosis is triggered, and the cell commits suicide. Researchers assume that this could be one of the reasons why radiation therapy or chemotherapy is sometimes ineffective. Both treatment methods cause severe damage to tumor cells, which eventually leads to programmed cell death. "If resistances occur, this is often caused by tumor cells 'refusing' to take the order to commit suicide," Thomas Hofmann explains. To prevent HIPK2 degradation, Hoffmann and his colleagues conducted experiments in which they blocked the Siah-1 enzyme. As a result, HIPK2 was able to accumulate even in cells that were only slightly damaged, and apoptosis was induced. "Cancer medicine might be able to make use of our discovery," speculates Hofmann. "For example, we could use a Siah-1 blocker simultaneously with chemotherapy or radiotherapy to get the cells back into the apoptosis program." Helmholtz Association of German Research Centres | |||||||||||||||||||||
|
Related Dna Damage News Articles Researchers discover atomic bomb effect results in adult-onset thyroid cancer Radiation from the atomic bomb blasts in Hiroshima and Nagasaki, Japan, in 1945, likely rearranged chromosomes in some survivors who later developed papillary thyroid cancer as adults, according to Japanese researchers. Heavy metal link to mutations, low growth and fertility among crustaceans in Sydney Harbor tributary Heavy metal pollutants are linked to genetic mutations, stunted growth and declining fertility among small crustaceans in the Parramatta River, the main tributary of Sydney Harbour, new research shows. Landmark studies assess risk of exposure to elevated levels of EMS confirm clear toxicity threshold New data from studies presented at the XVII International AIDS Conference in Mexico City have provided unprecedented insight into the toxicity of an impurity called ethyl methanesulfonate (EMS). The formation of the EMS impurity is a potential by-product of the manufacturing of mesylate salts, which are contained in over 40 drugs currently available worldwide. A new cellular pathway linked to cancer is identified by NYU researchers In the life of a cell, the response to DNA damage determines whether the cell is fated to pause and repair itself, commit suicide, or grow uncontrollably, a route leading to cancer. Once suspect protein found to promote DNA repair, prevent cancer An abundant chromosomal protein that binds to damaged DNA prevents cancer development by enhancing DNA repair, researchers at The University of Texas M. D. Anderson Cancer Center report online this week in the Proceedings of the National Academies of Science. Obese men have less semen, more sperm abnormalities, and should lose weight before trying for a baby Obese men should consider losing weight if they want to have children, a scientist told the 24th annual conference of the European Society of Human Reproduction and Embryology. Diabetes linked to male infertility; excess sugars in the body have direct effect on sperm quality Diabetes in men has a direct effect on fertility, a scientist told the 24th annual conference of the European Society of Human Reproduction and Embryology today. Couples with fertility problems where the man is over 35 have increased difficulty in conceiving Pregnancy rates decrease and miscarriages increase when a father is over 35 years of age, a scientist will tell the 24th annual conference of the European Society of Human Reproduction and Embryology. Sunburn alert: UVB does more damage to DNA than UVA As bombs burst in air this July 4, chances are that sunburn will be the red glare that most folks see - and feel. But unfortunately, even when there is no burn, the effects of the sun's ultraviolet (UV) rays can have deadly consequences. EuroDYNA takes lid off the genome European researchers have made significant progress unravelling how genes are governed and why this sometimes goes wrong in disease. More Dna Damage News Articles |
|||||||||||||||||||||
|
|||||||||||||||||||||
|
|||||||||||||||||||||