Myc's Cancer-Causing Joy Ride More Reckless than Previously Believed
October 07, 1999
Many drivers feel the urge to floor the accelerator on a crisp sunny day when the highway ahead seems to stretch straight to eternity. But only the most foolish would cut the brake line while pushing the pedal to the metal.
Yet one of the body's most potent cancer-causing genes does precisely that inside a cell, scientists at the University of Rochester Medical Center have found. The result of the unfettered molecular joy ride is, oftentimes, cancer. Details of the research are in the October issue of the Journal of the European Molecular Biology Organization (EMBO).
Scientists have long recognized that the protein produced by a gene known as myc spurs a cell to grow. Just like pushing the accelerator makes a car move forward, producing more myc makes a cell grow and divide. Too much myc spells an invitation to cancer, where cells grow uncontrollably and invade other tissues.
Now scientists have found that myc is even more powerful than they anticipated: The gene also has a role in disabling the molecular signals, the "brakes," that cells rely on to slow growth. When myc is out of control, not only is the accelerator floored but the brakes are out. It's no wonder that the gene plays a role in many human cancers, including those in the lung, colon, breast, bladder, and brain.
"Myc is central to our cells' ability to grow, divide, and even die when they should," says Hartmut Land, Ph.D., director of the University's Center for Cancer Biology and lead investigator of the EMBO study. "Basically, myc is like the starter of an engine; it's responsible for making the whole cell go. It's a very potent gene, but one that's been slow to yield its secrets. Myc has been a conundrum."
Land's team showed that myc controls another protein, cyclin D, known to play a big role in making cells grow; the EMBO paper marks the first time scientists have identified the "brains" behind cyclin D's actions. Land's team also found that cyclin D can not only accelerate growth, which has been known, but also knock out the proteins that a cell normally uses to put the brakes on growth, a surprising finding.
While Land says it's too early to know the implications of the work for cancer treatment, the findings mark another step in scientists' journey to unravel the amazing cell-signaling network that underlies our body's ability to produce cancer cells. That process is the focus of more than 100 scientists just joining the Center for Cancer Biology, a new effort begun by the University this year to study how faulty cell signals can conspire to cause cancer.
"Unraveling cell signaling is more or less like looking at a chess board and trying to figure out how the game is being played. What are the important rules? Who are the key players?" asks Land, who is the Robert and Dorothy Markin Professor of Cancer Biology.
"We're scratching the surface of a complexity that five years ago, nobody even dreamed about. The full texture of the biochemical circuitry of cells is just beginning to emerge, and that's exciting. Information like this helps us to understand how to manipulate cancer cells and ultimately should help us treat cancer in new and unexpected ways."
Land was one of the first to realize the immensity of the signaling network inside a cell, discovering in the early 1980s that multiple genetic changes are necessary for a cell to become cancerous. Much of his work has been done at the Imperial Cancer Research Fund in London, where Land did research before coming to the University this year.
Also contributing to the project research were Soo-Hyun Kim and Beatrice Griffiths of the Imperial Cancer Research Fund; Ignacio Perez-Roger, now at the Instituto de Biomedicina in Valencia, Spain; and Andreas Sewing, now with Smithkline Beecham Pharmaceuticals. The work was funded by the Imperial Cancer Research Fund and the European Community.