It has been extremely difficult to demonstrate that c-Myc-induced cell death really does suppress malignancy in animals, says Evan. Our new study is the long-awaited proof.
The finding is provocative, for during the last decade research has suggested that it takes a host of oncogenic missteps, accumulated in a multi-stage process, to prompt the panoply of events that lead to cancer. These events include uncontrolled cell proliferation; loss of ability to specialize, or differentiate; the development of a blood vessel system, or angiogenesis; and the migration and interaction of a tumor with neighboring cells and surrounding tissue.
The UCSF-led study calls this theory into question, says Evan. Our data demonstrate that complex cancerous tumors can be induced and maintained in the body at least the mouse body - by a simple combination of just two interlocking molecular lesions, he says. Once its lethal properties were suppressed by Bcl-xL, we could see that the c-Myc oncoprotein had the ability to orchestrate all of the other required attributes of cancerous cells, including generation of a blood supply. When c-Myc was turned off, the blood supply collapsed and all the tumors regressed.
The question, of course, is how often two such inter-linked mutations would occur. You have to have the right two lesions, working in combination, says Evan. c-Myc alone drives cell growth but this is overcome by cell death. Bcl-xL alone keeps cells alive but shuts down their growth. Only when you get the two together do you get this remarkable cooperation. The chances of two such mutations occurring together are very low, and this may be the fortunate reason that cancer cells arise so rarely in our bodies.
Evidence suggests that most, perhaps all, oncogenes have some form of
'"/>
Contact: Jennifer OBrien
jobrien@pubaff.ucsf.edu
415 476 2557
University of California - San Francisco
3-May-2002