[Editors] MIT sheds light on how tumor cells form

[Elizabeth Thomson]

MIT News Office
Massachusetts Institute of Technology
Room 11-400
77 Massachusetts Avenue
Cambridge, MA  02139-4307
Phone: 617-253-2700
http://web.mit.edu/newsoffice/www

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MIT sheds light on how tumor cells form
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For Immediate Release
WEDNESDAY, JUNE 21, 2006
Contact: Elizabeth A. Thomson, MIT News Office
Phone: 617-258-5402
Email: thomson at mit.edu

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CAMBRIDGE, Mass.--MIT cancer researchers have discovered a process 
that may explain how some tumor cells form, a discovery that could 
one day lead to new therapies that prevent defective cells from 
growing and spreading.

The work was reported June 8 in the advance online issue of The EMBO 
Journal, a publication of the European Molecular Biology Organization 
(EMBO).

Tumor cells that grow aggressively often have an irregular number of 
chromosomes, the structures in cells that carry genetic information. 
The normal number of chromosomes in a human cell is 46, or 23 pairs. 
Aggressive tumor cells often have fewer or more than 23 pairs of 
chromosomes, a condition called aneuploidy.

To date it has not been clear how tumor cells become aneuploid.

  "Checkpoint proteins" within cells work to prevent cells from 
dividing with an abnormal number of chromosomes, but scientists have 
been puzzled by evidence that aneuploidy can result even when these 
proteins appear to be normal.

What MIT researchers have discovered is a reason these checkpoint 
proteins may be unable to sense the defective cells, which tend to 
have very subtle errors in them. (These subtle errors are believed to 
be the cause of aneuploidy and the rapid growth of tumors.)

Before cells divide, individual chromosomes in each pair of 
chromosomes must attach to a set of tiny structures called 
microtubules. If they attach correctly, the checkpoint proteins give 
them the go-ahead to divide. If they don't, the checkpoint proteins 
are supposed to stop them from dividing.

"The checkpoint proteins are like referees in a tug-of-war contest," 
said Viji Draviam, a research scientist in MIT's Department of 
Biology and lead author of the paper. "They make sure that all 
chromosomes are lined up in the right places before the cell is 
allowed to divide."

Scientists have known about the function of checkpoint proteins for 
at least 20 years, and they have suspected that mutations in 
checkpoint proteins cause the irregular number of chromosomes in the 
aneuploid cells. But they have been perplexed by the infrequent 
occurrence of mutations in aneuploid tumors.

"It's puzzling that the suspected culprits - the aneuploidy-inducing 
checkpoint mutations - are rarely found at the scene of the crime, in 
the aneuploid tumors," Draviam said.

That lingering question prompted Draviam and her colleagues to study 
how two other key molecules - a known tumor suppressor protein called 
APC and its partner protein EB1 - work together to assure that cells 
divide normally.

They discovered that if they removed either protein from a cell or if 
they interrupted the way the proteins work together, the cell would 
become aneuploid. In other words, the checkpoint proteins need to 
sense that the APC and EB1 proteins both are present for normal cell 
division to take place.

"This is important because it is the first demonstration that 
interrupting the normal function of these proteins will cause the 
cell to become aneuploid," Draviam said.  "Our research sheds light 
on what could go wrong to cause an irregular number of chromosomes in 
cells even when the checkpoint proteins appear to be functioning 
properly."

Draviam's co-authors are graduate students Irina Shapiro and Bree 
Aldridge and MIT Professor of Biology and Biological Engineering 
Peter Sorger.

The research was funded by the National Institutes of Health.

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Elizabeth A. Thomson
Assistant Director, Science & Engineering News
Massachusetts Institute of Technology
News Office, Room 11-400
77 Massachusetts Ave.
Cambridge, MA  02139-4307
617-258-5402 (ph); 617-258-8762 (fax)
<thomson at mit.edu>

<http://web.mit.edu/newsoffice/www>
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