Team Led by UMass Amherst Researcher Implicates Gene in Susceptibility to Breast Cancer

August 9, 2000

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AMHERST, Mass. - A team of researchers at the University of Massachusetts has demonstrated that a gene, known to play a pivotal role in suppressing cancer cells, is compromised in normal breast cells. The findings were released in a recent issue of the journal Cancer Research. Although the relative inactivity of the protein in breast cells may trigger susceptibility to breast cancer, the researchers also demonstrate that the p53 protein can be activated by hormonal stimulation. The finding could spur the development of chemoprevention therapies for breast cancer. Members of the research team were UMass cancer biologist Joseph Jerry, graduate student Charlotte Kuperwasser and Bay State Medical Center pathologist Stephen Naber. The study was funded by the Massachusetts Department of Public Health and the National Institutes of Health.

The p53 gene is the focus of many research projects because it is commonly mutated in tumors, said Jerry. The healthy p53 gene -- often called the "tumor suppressor" gene -- spurs production of p53 protein, which in turn acts as the "police" of the cell, Jerry said. The protein monitors the cell to ensure that it is functioning properly. If a cell is damaged, p53 protein coordinates the activities that either repair it or kill it. Thus, if p53 is not functioning properly, the miscues on the cellular level may start a tumor. The team analyzed the protein in normal mammary tissue. Although the study was conducted on mice, similar results were observed in human tissues.

The major findings of the study include:

* The p53 protein is not fully functional in the normal mouse mammary;

* The p53 protein is not found in a cell''s nucleus, as was previously believed, but rather, in a cell''s cytoplasm;

* The discovery that exposure to hormones associated with pregnancy stimulated the protein''s function in cancer-fighting activities.

Scientists have long known that susceptibility to breast cancer is increased in women who reach puberty early, and have not had children, but the underlying molecular mechanisms of the disease are poorly understood, Jerry said. Heightened susceptibility during critical periods of breast development has been associated with certain cells that are unable to repair themselves after DNA damage; scientists suspect that failed DNA repair may be responsible for the increased incidence of breast cancer.

NOTE: Joseph Jerry can be reached at 413/545-2428.