UW-Madison researchers have discovered one way a gene that usually protects against tumors can, when mutated, spur cancers of the breast, ovaries, lung and bladder.
The finding involving the protein p53 — for which no drugs have been developed, despite its link to many cancers — could provide a target for drug development, the scientists said.
“If you can eliminate mutant p53, you might be able to eliminate cancers driven by p53,” Richard Anderson, one of the cancer researchers involved in the study, said in a statement.
“Our discovery of this new molecular complex points to several different ways to target p53 for destruction,” said Dr. Vincent Cryns, who also worked on the study.
The findings were published Monday in the journal Nature Cell Biology. Postdoctoral fellows Suyong Choi and Mo Chen also participated.
Tumor protein 53, or p53, located in cells throughout the body, serves as the “guardian of the genome,” according to the National Institutes of Health.
The protein repairs DNA damaged by radiation, toxic chemicals and ultraviolet rays from sunlight. When cells can’t be repaired, the protein prevents cells from dividing and signals them to die.
But in mutated form, the protein fails to control cell growth, leading to cancer. Mutated p53 contributes to 20 percent to 40 percent of breast cancers, nearly half of ovarian and lung cancers, and some cancers of the bladder, the head and neck, and other cancers.
Breast cancers with mutated p53 are more likely to be aggressive and resistant to treatment, and to return after treatment, according to the NIH.
In lab studies, the UW-Madison researchers discovered a mechanism that can drive mutated p53. They identified an enzyme, PIPK1-alpha, and a lipid messenger, PIP2, that regulate p53.
They also showed that when the PIP2 enzyme pathway is disrupted, mutant p53 doesn’t accumulate and cause damage.
The researchers are searching for molecular inhibitors of the enzyme that potentially could be developed as drugs to treat tumors involving p53 mutations.
The research was funded by the National Institutes of Health, the Department of Defense Breast Cancer Research Program and the Breast Cancer Research Foundation.