News Release

Protein inhibits colorectal cancer growth

Peer-Reviewed Publication

University of Toronto

Researchers have discovered a protein that suppresses colorectal cancer in mice and human cell cultures, according to a study in the Aug. 24 issue of Nature.

The researchers found that if the protein, called p110g, is absent it can cause spontaneous development of colorectal cancer in mice, and when it is present it stops tumour growth. It was a surprise discovery because they were examining how p110g regulates the movement of white blood cells in the immune system, not how it affects cancer cells.

"This is a completely novel and unexpected finding. It defines an entirely new field of inquiry," said senior author Professor Josef Penninger of immunology and medical biophysics at U of T, the Ontario Cancer Institute and the AMGEN Research Institute. "We were studying mice that were genetically engineered to lack the protein, and they started to get very sick and die. Soon we found they had invasive colorectal cancer. We never, ever would have expected that because every prediction about p110g had been that it actually caused cancer."

After this first indication that p110g suppressed tumour growth in genetically engineered mice in November 1999, the research team led by Penninger's postdoctoral fellow Takehiko Sasaki extended the study to human colorectal cancer cells taken from patients' tissue. They found no evidence of the protein in approximately 25 per cent of the colorectal cancer samples.

Then they investigated the results of putting p110g back in colorectal cancer cells that did not have it. The addition of the protein stopped tumour cell growth in the human cancer cell cultures, regardless of any other genetic mutations those cells had. "This is very hopeful because it means even if people have diverse mutations which predispose to colorectal cancer, our protein might have the possibility to shut them all down," Penninger said.

Finally, the researchers injected the human colorectal cancer cells into normal mice, who quickly grew tumours, and then added the protein to the cancer cells. Again, growth of colon cancer was suppressed. "These results are a good argument that this is the real thing and it is strong evidence for the protein's role in humans," said Penninger.

One of the next steps, Penninger said, will be to study the exact workings of the p110g system in colon cancer, which could lead to future drug therapies that replicate or stimulate the protein's action in stopping tumour growth. Researchers will also investigate whether some people have a genetic mutation that causes them to not have p110g and therefore be predisposed to colorectal cancer. Colorectal cancers are the second leading cause of cancer death and it is estimated that half of all people will develop colon tumours by age 70.

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Funding for the study was provided by AMGEN Inc., the National Cancer Institute, the Medical Research Council of Canada and CANVAC (Canadian Centre of Excellence for Vaccination).



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