'Off switch' for cell division found.

Certain cells in the body carry an "on switch" that enables them to begin dividing after a period of lying quiet. Researchers from the University of Connecticut in Farmington have now identified a corresponding "off switch." While their work is preliminary and does not at the moment present a way to turn off cancer cells, it does offer insight into the basic biology of cell reproduction.

Some cells constantly divide; others don't have the capability to divide at all. A third class, which includes liver cells, neurons and lymphocytes, can remain dormant for months or years, but when needed switch into a dividing state. Previous experiments have shown that dividing cells contain a "wak-up" factor, or activator, that promotes cell division by inducing DNA synthesis. The presence of an inhibitor has been suggested by other experiments showing that when resting and dividing cells are fused together, DNA production is somehow halted.

Janice K. Gutowski, Ann West and Stanley Cohen of UConn were able to extract a protein from resting white blood cells that inhibits DNA replication in cell nuclei stimulated by the activator. They describe the action of the protein in the August PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (No. 15). The researchers have since found that the inhibitor can not only prevent activation but also turn off already activated nuclei.

"The picture that's emerging is that DNA synthesis in dividing cells represents a balance between positive and negative factors," Gutowski says. "It may be that the balance controls a normal cell's growth."

What needs to be determined, she says, is just how the inhibition works--or, in the case of tumor cells, doesn't work. "The [tumor] nuclei may not be responsive to the inhibitor or the cells don't make it," she says. "Either way you'd get a loss of growth control." If the problem is in the manufacture, there may be ways to manipulate the system. "If we have a way of getting an inhibitor into the cell," she says, "it may be able to show tumor growth."

Manjusri Das of the University of Pennsylvania in Philadelphia, who did early work on cell activation, comments. "The research attacks an important issue." The question now, she says, is whether the protein is the key inhibitor, or whether its effect is a by-product of the experimental setup and does not play a role in the in vivo cell.