Navigation Links
Double trouble: Cells with duplicate genomes can trigger tumors

Abnormal cell division that yields cells with an extra set of chromosomes can initiate the development of tumors in mice, researchers at Dana-Farber Cancer Institute have shown, validating a controversial theory about cancer causation put forth by a scientific visionary 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," says David Pellman, MD, a pediatric oncologist at Dana-Farber and at Children's Hospital Boston. He is the senior author on a report in the Oct. 13 issue of Nature. Takeshi Fujiwara, PhD, and Madhavi Bandi of Dana-Farber, are the paper's co-first authors.

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.

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.

When injected under the skin of laboratory mice, about 25 percent of the animals developed breast cell tumors, and these tumors, like the tetraploid cells that seeded them, were also marked by similar chromosomal irregularities.

The new findings confirm a far-sighted notion of Theodor Boveri, a German scientist of the 19th Century who was one of the discoverers that the chromosomes in the nucleus of the cell carry the material of heredity, or genes. In 1914, he published what Pellman calls an "amazingly accurate and prescient" treatise suggesting, among other things, that genetic instability was a cause of malignant tumors.

One way to obtain this lack of chromosomal integrity, Boveri proposed, was a result of cells failing to divide normally, generating the double-value or tetraploid cells. Normally, human cells carry a "diploid" set of chromosomes ? that is, 22 pairs plus an "X" and "Y" chromosome in males and two "X" chromosomes in female. Tetraploid cells contain 44 pairs plus the sex chromosomes.

"Our experiments test an idea that's been percolating along among cell biologists for many years but was never really embraced by the cancer community," says Pellman. "We set up this experiment to test it in a real cancer setting."

A companion paper being published simultaneously in Nature by Randy King and colleagues at Harvard Medical School reports that tetraploid cells may arise more frequently than had been thought. According to Pellman, the instability of tetraploid cells may have played a role in evolution, because many organisms, including humans, are thought to have undergone ancient genome doublings.

The 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. " In other experiments, we identified genes in a model organism-- yeast-- that are essential for the survival of tetraploid cells but not for cells with a normal number of chromosomes" Pellman says. "You knock out those genes, and the tetraploid cells die. We are eager to find out if this can be extended to cancer cells and the new animal model should help us do this."


'"/>

Source:Dana-Farber Cancer Institute


Related biology news :

1. Affymetrix Unveils Plans to Double Plant and Animal Genome Microarray Offering
2. Double triumph in stem cell quest
3. Double the death rate from cirrhosis for blue collar men
4. Jump-starting T Cells In Skin Cancer
5. Emory Study Tests Bone Marrow Stem Cells to Improve Circulation in Legs
6. Transplantation Of Monkey Embryonic Stem Cells Reverses Parkinson Disease In Primates
7. Fundamental Finding Yields Insight into Stem Cells, Cancer; Opens Door to Drug Discovery
8. Weill Cornell Research Reveals Secrets Of Trafficking Within Cells
9. First-ever Compounds To Target Only Metastatic Cells Are Highly Effective Against Breast, Prostate, And Colon Cancers
10. Placenta Is A Rich Source Of Blood Stem Cells
11. UCSD Discovery Shows How Embryonic Stem Cells Perform Quality Control Inspections
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:11/19/2016)... , Nov. 18, 2016 Securus Technologies, ... solutions for public safety, investigation, corrections and monitoring, announced ... smaller competitor, ICSolutions, to have an independent technology judge ... the most modern high tech/sophisticated telephone calling platform, and ... customers that they do most of what we do ...
(Date:11/15/2016)... , Nov 15, 2016 Research and Markets ... Forecast to 2021" report to their offering. ... ... 16.18 Billion by 2021 from USD 6.21 Billion in 2016, growing ... Growth of the bioinformatics market is driven by the growing ...
(Date:6/22/2016)... ANGELES , June 22, 2016 /PRNewswire/ ... identity management and verification solutions, has partnered ... edge software solutions for Visitor Management, Self-Service ... provides products that add functional enhancements ... partnership provides corporations and venues with an ...
Breaking Biology News(10 mins):
(Date:12/8/2016)...  Biotheranostics today announced that new data will ... Cancer Index (BCI) in identifying which patients with ... for disease recurrence and might benefit from extended ... advancing the understanding of the value of BCI ... inform decisions related to patient treatment. These data ...
(Date:12/8/2016)... Portland, Oregon (PRWEB) , ... December 08, 2016 ... ... modules and the FrontPanel SDK that provide essential device-to-computer interconnect using USB or ... do not require FrontPanel support. The FOMD-ACV-A4 is a small, thin, SODIMM-style module ...
(Date:12/8/2016)... ... 08, 2016 , ... KBioBox llc announced today the launch ... developed a sophisticated “3 click” gene dditing off target analysis program and a ... https://www.kbiobox.com/ and powered by the company’s proprietary BioEngine. Scientists, pharmaceutical ...
(Date:12/8/2016)... N.J. , Dec. 8, 2016  Soligenix, ... late-stage biopharmaceutical company focused on developing and commercializing ... an unmet medical need, announced today the long-term ... with SGX942 (dusquetide), a first-in-class Innate Defense Regulator ... in head and neck cancer patients undergoing chemoradiation ...
Breaking Biology Technology: