Tumor-Suppressing Gene Pinpointed
Scientists have identified a gene that helps protect mice against intestinal tumors, although it may also play a role in spreading breast cancer, according to a study published on Thursday.
Despite the gene’s Jekyll-and-Hyde personality, the discovery may one day lead to drugs that boost resistance to cancer in humans, said the study, which appears in the British journal Nature.
Researchers led by Roger Reeves at Johns Hopkins University in Baltimore, Maryland, showed that the gene Ets2 acts as a tumor suppressor in rodents afflicted with the human equivalent of Down’s syndrome.
The finding settles a decades-old debate about whether this inherited disorder confers protection against cancerous tumors.
Establishing this connection was, in fact, the starting point for a clever series of experiments using genetically modified mice that eventually led to Ets2.
Down’s syndrome, which occurs in approximately one in 800 live births, retards physical and intellectual development. Persons with the syndrome have an extra chromosome in their genetic code – 47 rather than 46, due to an additional 21st chromosome.
Reeves and his colleagues began by cross-breeding rodents carrying the three copies of chromosome 21 with another set of gene-altered mice designed to develop intestinal cancer.
Compared to normal mice, the offspring produced far fewer tumors, and the cancers that did appear were smaller, the study showed.
Further breeding experiments led to a third mutant mouse that expressed the minimal genetic changes needed to produce Down’s syndrome, and this allowed Reeves to narrow down the precious anti-tumor source to a mere 33 genes.
He then created a new mouse variant with only a single copy of these 33 genes and mated it with cancer-producing rodents.
As expected, the resulting offspring showed a significant increase in tumors, which suggests that the gene (or genes) that protect against malignant growths are more effective when there are multiple copies of them.
This explains, Reeves concluded, why individuals with Down’s syndrome – who have an extra copy of the chromosome containing the genes in question – would have lower rates of cancerous growths.
The final step in the lab detective work was to narrow the tumor-buster down even further.
In the end, only one gene correlated perfectly with the incidence of tumors in the mutant mice – Ets2.
This surprised the researchers, because increased activity of the Ets2 protein has been previously linked to the spread of breast cancer.
Resolving this paradox, says David Threadgill, a geneticist at the University of South Carolina, will be vital if drugs with Ets2-like action are to be harnessed in the fight against cancer.Filed under: Health