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Dartmouth Medical School Dartmouth-Hitchcock Medical Center


When good cells go bad

By Amos Esty

Compton, left, and Thompson study chromosome missegregation in tumor cells.

Two DMS biochemists have identified a link between a tumor suppressor gene and a crucial step in cell division. During cell division, cells copy their chromosomes and then split them evenly between two "daughter" cells. This process—chromosome segregation—usually goes smoothly. But about one in every hundred divisions, a chromosome missegregates; it ends up in the wrong daughter cell, leaving one daughter cell with too many chromosomes and one with too few, a condition called aneuploidy. One in a hundred sounds like a successful rate, says Duane Compton, Ph.D. "But when you consider that in our bodies there are tens of millions of cells that divide every minute, one in a hundred is pretty bad actually."

Potent: Aneuploidy is common in tumors and can indicate a poor prognosis. But as Compton and graduate student Sarah Thompson already knew, something often prevents aneuploid cells from proliferating. "We wanted to understand what was happening to those aneuploid cells," Thompson says. They hypothesized that a tumor-suppressor gene, p53, might play a role. Compton says p53 is "very potent. . . . When it gets activated, it just shuts down the cell cycle."

To test that hypothesis, Compton and Thompson induced cells from human tissues to missegregate chromosomes and measured p53 levels in the resulting cells. They found higher levels of p53 in aneuploid cells than in normal cells. And as expected, the aneuploid cells did not continue to grow and divide. But when they knocked out the p53 gene, preventing cells from producing the p53 protein, they found that even aneuploid cells were able to continue to divide.

Next, they combined a loss of p53 with elevated rates of chromosome missegregation and found that this combination produced cells that resemble tumor cells. "In essence, we can convert a normal cell into what looks like an aneuploid tumor cell," Compton says. Eventually, this knowledge may help the researchers find a way to prevent aneuploid tumor cells from growing and dividing.

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