NEW YORK, Jan. 12 (UPI) -- U.S. experts said Friday they have learned secrets of why tumor suppressor genes stop working in diseases like breast and colon cancer.
Scientists at Memorial Sloan-Kettering Cancer Center in New York found that a protein, identified as NEDD4-1, eliminates the tumor suppressor gene PTEN by adding a molecular tag to the gene. That tagging causes a molecular cascade resulting in the destruction of the gene.
Zuejen Jiang and colleagues at Sloan-Kettering discovered that in a mouse model for prostate cancer, animals with aggressive tumors had low levels of PTEN but high levels of NEDD4-1. They concluded that by downregulating PTEN, NEDD4-1 promotes growth of prostate cancer.
The findings are reported in Friday's issue of the journal Cell.
A second team of Sloan-Kettering investigators led by Pier Paolo Panndolfi in a companion article described another aspect of how PTEN is affected by NEDD4-1. He found that PTEN levels in the cell nucleus are reduced, especially in certain colon-cancer patients.
The researchers said the work suggests that targeting cancers that have the PTEN mutated genes with drugs known as proteasone inhibitors could be helpful in fighting the disease. The drugs slow or prevent PTEN from being degraded, thereby strengthening the gene's ability to mobilize a fight against the cancer.
The research was supported by grants from The National Institutes of Health and the American Cancer Society.
