Vol. 12, No. 2,856W - The American Reporter - March 18, 2006


WHY SOME PATIENTS WON'T SURVIVE WHEN CANCER STRIKES
by Mark Perew
American Reporter Science Correspondent
Santa Ana, Calif.

NEW YORK -- A small gene on human chromosone 4 has a big say in who=

survives cancer.

That gene, which carries the cryptic name MAD2, is a sequence of so= me 600 base pairs that that has the job of producing a complex protein comp= osed of about 200 amino acids.

It also may make the difference between life and death if youdevelo= p cancer.

In 1996, doctors from the Memorial Sloan-Kettering Cancer Center he= re discovered that MAD2 controls cell reproduction. Now they believe they = know why, and more importantly, they know it plays a role in some cancers. = The researchers' work will be published in this week's edition ofthe= journal Nature.

When cells divide, several mechanisms keep them from dividing toofa= st or too often. The MAD2 gene is one of those; as long as the MAD2gene is= present and producing the right protein, one part of cell divisionis under= control.

But doctors say that when MAD2, is missing things get out of handin= a hurry. Even having just one copy of MAD2, instead of the normal two,can= lead to problems.

A group of 10 doctors from Sloan-Kettering and Columbia Universityi= n New York, the Robert H. Lurie Comprehensive Cancer Center in Chicagoand t= he Massachusetts Institute of Technology in Cambridge, Mass., havestudied M= AD2 and come up with some promising discoveries.

Using yeast, mice and human cells, which all have the MAD2 gene,the= se scientists now understand how and when MAD2 works and what goeswrong whe= n it's absent.

During the process of mitosis, or cell-splitting, chromosomes = gothrough some unusual steps. They emerge from a tight bundle in thenucleu= s and arrange themselves like a group of suspects in a policeline-up. Befo= re the chromosomes divide, MAD2 works to stop any cells thatmight have beco= me defective. When, for reasons associated with one'sgenetic heritage, MAD= 2 isn't there to do the job, events can go awry.

At this point in the process of making more cells, sometimes a= nextra chromosome pops up or one disappears, a condition scientists callane= uploidy (an-u-ploy-dee). MAD2 should cause that cell to die quicklybefore = that mistake, a mutation, can go on to reproduce itself. In cellswithout t= wo copies of the MAD2 gene, that check doesn't occur. Even incells with on= ly one copy the checking isn't done correctly.

"The aneuploidy appears random to us," Dr. Robert Benezra told= theAmerican Reporter. Dr. Benezra is one of the investigators who discove= redthis gene in humans and participated in the new research.

"Biolog= y will select for those changes that make the cell growmore aggressively," = he said. "Those changes that make the cell non-viablewon't be passed on."

That's the cancer connection. Cancers are aggressively growin= g,dividing, reproducing cells. When the MAD2 check fails, then a cancer is= more likely.

Not only is it more likely, but the cancer can be more resista= ntto a class of chemotherapy drugs called taxanes. These drugs work at the= level of cell division to slow down or even stop the growth of thecancerous= cells. The research group found that cells lacking one or morecopies of M= AD2 just don't respond well to this common class of drugs.

The sad news is that this discovery will allow doctors to know= which cancer patients are less likely to respond to chemotherapy,permitting= them to be more direct with their patients when explainingtheir chances of= survival.

The good news is that one day we may have a way to add MAD2 to= DNAin cells. Although that technology is not available now, other molecul= arbiologists are actively working on ways to insert such genes into theblue= prints of human life.

Mark Perew is a member of the National Association of Science Writers. = Write to him at perew@freeshell.org.

Copyright 2006 Joe Shea The American Reporter. All Rights Reserved.

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