The new finding offers a possible explanation for Evans long-standing question of why cancer is so relatively rare: c-Myc is likely to be mutated in one or other of the hundred thousand billion cells in our bodies hundreds of times each day. If such cells immediately start to expand, we might expect cancers to be arising all the time. Cancers should be very common, when in fact they are amazingly rare. Over an entire lifetime, only one in three people develop cancer, even though each of us has trillions of cells, each of which could become a tumor cell. This means that there must be something that prevents genes like c-Myc, when they get activated, from inevitably and immediately forming cancers. The propensity of proteins like c-Myc to induce apoptosis provides a key to this puzzle. Genes like c-Myc are booby-trapped: when activated out of context, they trigger cell death and can only drive cell proliferation in the right place at the right time.
Details of the study:
The researchers conducted their study in mice, specifically in the pancreatic beta cells, which produce insulin. When c-Myc was activated, the cells initially began to proliferate uncontrollably. However, the c-Myc booby trap then activated and the developing tumor mass rapidly disintegrated. Scientists have known that while c-Myc induces cell proliferation, it also has the potential to trigger cell death in cells that proliferate inappropriately and in the wrong tissue environment. However, this theoretical safety valve has never been observed before in a living tissue.
The researchers then went on to show that when they inhibited the ability of c-Myc to induce cell death (apoptosis) by introducing expression of a second oncoprotein called Bcl-xL, the proliferating cells immediately developed into a cancerous mass. Finally, however, in a finding that offers a new hope for therapy, they showed that when c-
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Contact: Jennifer OBrien
jobrien@pubaff.ucsf.edu
415 476 2557
University of California - San Francisco
3-May-2002