October 13, 2005
Double trouble: Cells with duplicate genomes can trigger tumorsTopics: Medicine
In a study that confirms a century-old theory about cancer causation -that genetic instability was a cause of malignant tumors, researchers at the Dana-Farber Cancer Institute have shown that abnormal cell division that yields cells with an extra set of chromosomes can initiate the development of tumors in mice. This validated a controversial theory about cancer causation put forth by Theodor Boveri, a German scientist and scientific visionary, that he proposed nearly 100 years ago.
The so-called "double-value" cells are produced by random errors in cell division that occur with unknown frequency. The generation of these genetically unstable cells appears to be a "pathway for generating a tumor.As addressed in the article, therapeutic implications arise from biological differences between the tetraploid cells and normal cells that might make the tetraploid-derived cancerous cells vulnerable to doses of drugs that aren't harmful to the normal cells and tissues.
The researchers treated normal breast cells with a compound that interfered with the final step of cell division, causing many of them to have the extra chromosome set. To make the cells more likely to become malignant, the researchers used cells that lacked a protective gene, p53 that is inactivated in many forms of cancer. Compared with normal breast cells, the double-value cells tended to be genomically unstable.
The research was performed in experimental animals, but such "double-value" cells are seen in a variety of early human cancers and in a precancerous condition called Barrett's esophagus. In addition to the extra chromosomes, the "double value" or "tetraploid" cells also duplicate a cell structure called the centrosome that plays a role in maintaining a stable genome. The extra centrosomes may be at the root of the cancer-triggering process. Once the genetic instability sets in, tumors "evolve " by losing, gaining and rearranging chromosomes.
Late-stage tumors commonly have too many centrosomes and a near triploid chromosome number (one and a half times the normal chromosome content). Because the cells with extra chromosomes and centrosomes are biologically different from normal cells, cancer drugs designed to kill them while sparing normal cells are "an interesting possibility," says Pellman, who is also an associate professor of Pediatrics at Harvard Medical School.
Future studies will be conducted to determine if the researchers can apply the already determined fact that knocking out the genes responsible for the survival of tetraploid cells results in their death - to cancer cells.
Posted by Richard at October 13, 2005 12:39 AM
Articles Related to Medicine: