Cancer gene linked to lupus-type disease in mice
September 23, 1999
Web posted at:
3:00 p.m. EDT (1900 GMT)
By Christine Cosgrove
(WebMD) -- A gene known to cause cancer may also be responsible for some autoimmune diseases, according to a new laboratory study of mice.
For nearly three years, scientists have accumulated evidence showing that mutations in this gene, known as PTEN, are linked to many different types of cancers in humans.
In this week’s issue of the journal Science, researchers at Memorial Sloan-Kettering Cancer Center in New York reported that a mutation in one of the two pairs of PTEN genes in mice allowed certain white cells, called lymphocytes, to proliferate unchecked. This proliferation eventually resulted in the lymphocytes attacking the organs of the mice, a characteristic of autoimmune disorders such as lupus.
As the cells accumulate further damage in their genes, malignant tumors begin to grow, wrote the study's lead author, Antonio Di Cristofano of Memorial Sloan-Kettering's Cancer Center.
The PTEN gene is beginning to rival gene P53, which has been implicated in a wide array of cancers. Mutations of PTEN have been found in human cancers of the brain, breast, prostate, endometrium, ovary and colon, as well as in melanomas and lymphomas, according to the research team.
It is too soon, however, to say whether people who have a defective PTEN gene and who also have an autoimmune disorder, such as lupus, have a greater risk of developing cancer, said Dr. Pier Paolo Pandolfi, principal investigator of the study and head of the Molecular and Developmental Biology Laboratory at Memorial Sloan-Kettering.
"It's important to remember that we were looking at mice, not humans," he cautions.
If further study proves that PTEN mutation acts in humans as it does in mice, the gene would become an important target for drug development, suggested Gerard Evan, a professor of cancer biology at the University of California, San Francisco. He added that the researchers' findings "point the finger very firmly at PTEN" in a number of diseases.
The human body has a complex system for regulating its cells, telling them when to divide, when to differentiate and, very importantly, when to die, he says.
"A cell that's dead is less of a problem than a cell that stays alive doing something you don't want it to do," explains Evan. "If a cell is born that can't die or is doing the wrong thing, you want to trash it. That's true of cancer cells, cells infected with viruses, cells making immune compounds that kill your own tissues, or cells that are in the wrong place."
And telling a cell when to die is what healthy PTEN genes do. But when they malfunction, cells don't die when they should. Instead, they proliferate and, if the mice studies hold true for humans, these "never-say-die" genes go on to cause disease.
In autoimmune diseases, the body's immune system becomes confused and instead of protecting the body from foreign invaders, it attacks the body's own tissues.
The list of autoimmune diseases includes certain blood diseases, as well as multiple sclerosis, lupus, rheumatoid arthritis and scleroderma. The list continues to grow as researchers identify autoimmune processes at the root of more illnesses.
But for now, with a test for the PTEN mutation already available, Pandolfi says his findings could lead to better prognosis and treatment for patients with precancerous conditions. For example, men with benign prostate disease could learn if they are at greater risk for developing prostate cancer if defects in their PTEN gene are detected.
People who test positive for the mutation could also be screened more frequently for various cancers, which would allow the disease to be caught sooner and treated earlier, suggested Pandolfi. Similarly, the status of a patient's PTEN genes may help doctors decide whether to treat a cancer aggressively or not.
Copyright 1999 WebMD, Inc. All rights reserved.
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