Printer Friendly

New gene ties cancer, cell cycle.

Three research groups seeking genes in different ways for very different reasons have discovered one that helps explain the development of cancer. The gene, which goes by at least three names, leads to the production of a protein that keeps cells in a resting, nondividing stage of the cell cycle. It is regulated by a tumor suppressor gene, called p53, already known to be important in keeping some cells from forming tumors (SN: 6/5/93, p.356).

"[The gene] is a missing piece [that explains] a lot of things that we didn't understand before," says James R. Smith of Baylor College of Medicine in Houston.

The new results indicate that when p53 fails to do its job, the cell stops making this new gene's protein, setting the stage for cancer. "[The results) provide a direct link between a tumor suppressor protein and the cell cycle," comment Tony Hunter, a molecular biologist at the Salk Institute in La Jolla, Calif.

Figuring out how p53 regulated the cell cycle "was sort of the Holy Grail in the tumor suppressor field," adds J. Wade Harper, a Baylor biochemist.

Smith and his colleagues had wanted to understand why old ceHls lose their ability to divide. They inserted pieces of DNA derived from nondividing, sensecent cells into young cells that were rapidly dividing in a laboratory dish and monitored with DNA stopped cell division.

Three DNA strands has this effect on the cells. The researchers isolated a gene from the strand most active in older cells, naming it senescent-cell-derived DNA inhibitor 1 (SDI-1) because it interfered with the synthesis of new DNA. The team will report its results in an upcoming EXPERIMENTAL CELL RESEARCH.

SD1-1 turned out to be the same gene that Harper and his colleagues, located just one floor away, had uncovered while investigating genetic regulation of the cell cycle. That group had called the gene CIP1. Then a casual phone conversation between BoylorNs Stephen J. ElledgeXand Bert Vogelstein of Johns Hopkins School of Medicine in Baltimore led to the realization that Vogelstein's team also had this gene in hand, under the alias of WAF1.

"We were the first two people to have a model of how p53 worked," Elledge recalls. "It was really quite a moment when we figured this out."

Vogelstein had known that the p53 protein exerts its tumor-suppressing effect indirectly, by regulating the activity of other genes. Using brain tumor cells grown in a laboratory dish, he and his colleagues determined that WAF1 turned on in the presence of normal p53 genes but not in the presence of mutant p53, they report in the Nov. 19 CELL.

The addition of lots of WAF1 to brain, lung, and colon tumor cells lacking functional p53 stops the cells' uncontrolled growth, notes Hopkins' Watik S. El-Deiry. Also, their data show that human p53 activities rodent WAF1, demonstrating that these genes and their proteins have been conserved through evolution.

While the Hopkins group was figuring out how p53 works, Harper and Elledge were trying to understand the link between the cell cycle and cancer. They developed a screening test to determine what controlled the activity of a cyclin-dependent kinase enzyme. This enzyme and others like it link up with proteins called cyclins, and together these molecules push a cell to start dividing.

The researchers screened for CIP1 by adding different pieces of human DNA to genetically engineered yeast. Genes essential for the yeast's survival would turn on only when the added DNA caused the yeast to produce a protein that bound to cyclin-dependent kinase, also a protein. Other work had already implicated the CIP1 protein En cell devision.

The discovery illustrates the power of this new screening technique, which enables scientists to elucidate protein-protein interactions, says Elledge.

Next, Harper and Elledge determined that in a laboratory dish, CIP1 virtually shut down the chemical activity of the cyclin-dependent kinase. Further tests showed that the CIP1 protein fid not keep the kinase from attaching to cyclin but did make the pair ineffective in stimulating celL division, they report in the Nov. 19 CELL.

Cells typically posses this built-in check on cell division. But when p53 malfunctions, "the cell can no longer make sufficient levels of the inhibitor to stop the cell cycle," Harper suggests.

"I think this idea of negative regulators is going to be an important one," says Hunter. However, he and the Hopkins group caution that this gene and its protein, whatever it name, may not be the critical target or may be just one of several targets of p53 and other regulators of cell division.

Even so, these scientists say they hope the discovery will lead to new anticancer therapies.
COPYRIGHT 1993 Science Service, Inc.
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 1993, Gale Group. All rights reserved. Gale Group is a Thomson Corporation Company.

Article Details
Printer friendly Cite/link Email Feedback
Author:Pennisi, Elizabeth
Publication:Science News
Date:Nov 27, 1993
Previous Article:Lasagna: a new recipe for 'dirty' soils.
Next Article:Dioxin linked to reproductive disorder.

Related Articles
First cancer-protecting gene characterized.
Cancer gene gap mapped.
Exposing lung cancer as a genetic disease.
Genetic roadblocks: the body may not always resist cancer, but it does have built-in barricades to slow the spread.
'Missing link' to cancer is found.
'Knockout' ties cancer gene, kidney growth.
Genetic flaw causes double trouble.
Bombs away against cancer cells.
Newfound gene linked to several cancers.
Cancer cells on the move.

Terms of use | Copyright © 2016 Farlex, Inc. | Feedback | For webmasters