Mayo Clinic discovers two key players in cancer prevention and how they work

December 14, 2005

ROCHESTER, Minn. -- Mayo Clinic researchers have challenged the conventional teaching about a common cancer trait and in doing so, discovered how cells are naturally "cancer proofed." Their findings appear in today's early online edition of the Dec. 15 issue of the journal Nature ( ).

The researchers investigated aneuploidy (AN-u-ploy-dee), the state in which a cell has an abnormal number of chromosomes that creates cellular instability, giving rise to tumors. They discovered two key proteins that help prevent aneuploidy, and also found how the proteins work to "cancer proof" a cell: by preventing premature segregation of duplicated chromosomes during (nuclear) cell division.

Significance of the Mayo Clinic Research

These new cancer players comprise a two-protein complex Rae1-Nup98. This complex works together to stabilize healthy cells by functioning as a kind of cell-division auditing system that makes sure the right number of chromosomes is distributed in each part of a newly divided cell. By so doing, they promote "euploidy" -- the ideal chromosomal distribution needed for stability, and the opposite of aneuploidy.

"What we discovered is that there's an active process of cellular machinery that prevents aneuploidy," says Mayo cancer researcher Jan van Deursen, Ph.D., who led the research team. "It's a surveillance mechanism involving the two proteins Rae1-Nup98 that makes sure that in every cell division the proper number of chromosomes occur."

Dr. van Deursen says the findings help set the stage for the development of a new generation of cancer treatments that are more effective and gentler than the current radiation and chemotherapy treatments used. "The reason we are investigating this in the first place is because 95 percent of all human cancers involve aneuploidy," he says. "When researchers show -- as we have just done -- new mechanisms that prevent aneuploidy, we are helping improve the understanding of the basic science that we hope will lead to new cancer treatments one day."

Background Biology

*A mutation in a cell's DNA can lead to tumor development by turning off the body's natural tumor suppression genes, or by turning on oncogenes -- special genes that promote cancer. For example, in at least 15 forms of human leukemia, Nup98 is found to be mutated.

*Aneuploidy plays a role in most cancers by making them unstable so they grow out of control. For years in labs around the world experiments using aneuploidic mice versus normal mice showed that if both groups are exposed to carcinogens, both groups develop tumors. But the aneuploidic mice get significantly more tumors. That prompted the urgent question the Mayo Clinic investigators set out to answer: How does aneuploidy arise?

*Until now, standard teaching held that aneuploidy's mechanism of action was controlled by a single cellular system. The Mayo discovery challenges and revises this by proving a second aneuploidy regulatory system is at work: the Rae1-Nup98 complex.

How Mayo Discovered the Importance of Rae1-Nup98

Errors in one step of cell growth can undermine the entire process. The Mayo researchers saw this happen when they used specially bred mice and lowered the amounts of the two proteins Rae1-Nup98 -- which were not previously known to be involved in aneuploidy regulation. The results: Insufficient Rae1-Nup98 threw off the timing of the cell growth process that correctly distributes chromosomes. Low Rae1-Nup98 caused three crucial missteps:
Collaboration and Support

The Mayo research team also included co-authors Karthik Jeganathan and Liviu Malureanu, M.D. Their work was supported by grants from the National Institutes of Health.

Mayo Clinic

Related Chromosomes Articles from Brightsurf:

Cancer's dangerous renovations to our chromosomes revealed
Cancer remodels the architecture of our chromosomes so the disease can take hold and spread, new research reveals.

Y chromosomes of Neandertals and Denisovans now sequenced
An international research team led by Martin Petr and Janet Kelso of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, has determined Y chromosome sequences of three Neandertals and two Denisovans.

Female chromosomes offer resilience to Alzheimer's
Women live longer than men with Alzheimer's because their sex chromosomes give them genetic protection from the ravages of the disease.

New protein complex gets chromosomes sorted
Researchers from the University of Tsukuba have identified a novel protein complex that regulates Aurora B localization to ensure that chromosomes are correctly separated during cell division.

Breaking up is hard to do (especially for sex chromosomes)
A team of scientists at the Sloan Kettering Institute has discovered how the X and Y chromosomes find one another, break, and recombine during meiosis even though they have little in common.

Exchange of arms between chromosomes using molecular scissors
The CRISPR/Cas molecular scissors work like a fine surgical instrument and can be used to modify genetic information in plants.

How small chromosomes compete with big ones for a cell's attention
Scientists at the Sloan Kettering Institute have solved the puzzle of how small chromosomes ensure that they aren't skipped over during meiosis, the process that makes sperm and egg.

GPS for chromosomes: Reorganization of the genome during development
The spatial arrangement of genetic material within the cell nucleus plays an important role in the development of an organism.

Extra chromosomes in cancers can be good or bad
Extra copies of chromosomes are typical in cancerous tumor cells, but researchers taking a closer look find that some extra copies promote cancer growth while others actually inhibit cancer metastasis.

X marks the spot: recombination in structurally distinct chromosomes
A recent study from the laboratory of Stowers Investigator Scott Hawley, PhD, has revealed more details about how the synaptonemal complex performs its job, including some surprising subtleties in function.

Read More: Chromosomes News and Chromosomes Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to