Mutated Gene Attacks Organs

A mutated gene that already has been linked to cancer in humans has now been found in mouse studies to cause the immune system to attack organs in the body.

The gene, called PTEN, normally combats cancer by killing abnormal cells that could form tumors. But when one of the normal pair of PTEN genes is missing or flawed, the single mutation can trigger cancer or cause white blood cells to damage the kidneys and other organs, researchers found.

"Our study shows that the loss of just one PTEN gene is enough to ... begin the process of uncontrolled cell growth (cancer)," said Dr. Pier Paolo Pandolfi of Memorial Sloan-Kettering Cancer Center in New York. He is the senior author of a study appearing Friday in the journal Science.

Pandolfi said the study also showed the PTEN gene mutation can cause the immune system to attack the body, a process known as autoimmune disease.

PTEN is one of a number of gene pairs that help to eliminate cells that are at risk of converting to cancerous growths. The genes work by causing the flawed cell to kill themselves, a process called apoptosis. For most gene pairs, both copies must be lost or mutated for cancer to result.

But Pandolfi said experiments with laboratory mice show that the loss of only one copy of the PTEN gene is enough to lead to cancer.

Loss of the one PTEN gene also causes an accumulation of white blood cells, or lymphocytes. These cells normally attack bacteria that invade the body. But Pandolfi said the mouse studies show that when PTEN is mutated, the lymphocytes start attacking organs in the body.

In mice bred with the PTEN mutation, the lungs, kidneys, spleen and other organs became enlarged and inflamed. Eventually, the mice died from a disease process that is similar to lupus, a disease often fatal in humans, said Pandolfi.

Although PTEN mutation has been linked to a number of human cancers, it has not been determined if the mutation is also present in patients with lupus. Pandolfi said he and his team are now looking for the PTEN mutation in DNA samples from lupus patients.

If it is shown that the mutation is present in lupus, he said, it might then be possible to develop a drug that blocks effects of the gene mutation.