A protein that can stop the growth of human bowel cancer cells -- in the test tube at least -- is reported in Nature1. Mice bred to lack this protein develop cancers of the colon and rectum, suggesting that the protein is vital for healthy bowel cells.

Bowel cancer is one of the biggest killer diseases of old age -- it is the second largest cause of cancer death. Half of those people who live to seventy develop tumours of the colon or rectum.

Until now the biochemical changes that cause colon cells to mutate, migrate and proliferate have not been known. Josef Penninger and his colleagues from the Ontario Cancer Institute, Canada, now report that one cause might be the absence of a protein: 'p110γ'.

p110ðg is part of a larger protein -- cumbersomely known as a 'Phosphoinositide-3-OH kinase or 'PI(3)K'. At first, Penninger's team thought that p110γ and PI(3)K were involved in the immune system because mice that lacked p110γ had altered levels of immune cells2. But they then noticed that older p110γ-knockout mice developed colorectal cancers.

When the researchers looked at human colorectal cancer cells they found that p110γ was often absent. And chemicals that encourage cell growth were abnormally abundant in the knockout mice and in human cancer cells.

In fact, when the gene 'p110γ' that codes for the p110γ protein was reinserted into the human colorectal cancer cells by genetic engineering, the levels of growth-promoting substances declined and the cells grew much more slowly. Results which are "impressive and surprising," according to cancer expert Bert Vogelstein of the Howard Hughes Medical Institute, Baltimore.

What exactly p110γ does is a mystery. "Because PI(3)K is involved in so many different cellular processes, I would have predicted more widespread changes to result from the lack of p110γ," comments Ray DuBois of Vanderbilt University, Nashville. "It was also surprising that insertion of a mutant [p110γ gene] caused a reduction of [cancer] cell growth similar to the effect of inserting normal p110γ."

"These results provide evidence of yet another molecule and signal pathway that is critical in the development and progression of colon cancer," says Anil Rustgi of the University of Pennsylvania.