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UCSF finding offers provocative insight into what drives cancer

In a finding that calls into question a prevailing belief about the way in which cancers develop and progress, researchers led by a UCSF scientist report that it may take only two interlocking genetic steps to cause tumors to develop.

In their study, published in the May 3 issue of Cell, the researchers focused on a protein known as c-Myc, which is produced by the c-myc oncogene. Oncogenes are a class of genes that stimulate normal cell growth but, when damaged, or mutated, send a cell into replication overdrive, the hallmark of cancer. The c-myc oncogene is activated in most human cancers. The current study is focused on the c-Myc protein, but the researchers predict that the phenomenon they observe will be emblematic of what occurs with other oncoproteins, too.

In their study, which involved inserting a switchable form of the human c-Myc oncoprotein into the pancreatic cells of live mice, the scientists made three important discoveries: First, they determined that c-Myc harbors a key cancer-preventing mechanism the ability to cause cell death, or apoptosis. Second, they determined that thwarting this mechanism by activating another oncoprotein, known as Bcl-xL, caused full-blown cancers. Finally, they showed that switching off the c-Myc protein triggered the collapse of robust cancerous tumors -- and the blood vessels fueling them.

The results we saw were dramatic, says the senior author of the study, Gerard Evan, PhD, the Gerson and Barbara Bass Baker Distinguished Professor of Cancer Biology at The University of California, San Francisco. Suppressing the cell-suicide pathway in c-Myc triggered the immediate growth of invasive, angiogenic tumors, while turning off c-Myc caused collapse of the tumors and rapid regression of the vasculature and invasiveness that support a metastatic tumor.

Scientists have known that c-Myc has a cell-suicide mechanism, and have presumed that it serves as a safety valve, kicked into action when c-My
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Contact: Jennifer OBrien
jobrien@pubaff.ucsf.edu
415 476 2557
University of California - San Francisco
3-May-2002


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