'Destruct' triggers may be jammed in tumor cells, UF geneticists say

GAINESVILLE, Fla. — Tumor cells living in the cross hairs of radiation or chemotherapy may be able to escape death because their self-destruct mechanisms are jammed, say University of Florida scientists writing in a recent issue of Developmental Cell.

Scientists studying fruit fly cells discovered that slight changes in the protein scaffolds that support the genes “reaper” and “hid” — aptly named for their roles in triggering cell death — cause the cells to become naturally resistant to X-rays during early development.

“It turns out that a piece of DNA that is required for mediating this process of cell death is blocked,” said Lei Zhou, Ph.D., an associate professor of molecular genetics and microbiology in the UF College of Medicine. “When it is blocked, the cells just don’t die, even when subjected to heavy doses of radiation. This may be what is happening in some resistant cancer cells. The pro-apoptotic genes cannot be induced to cause cell death.”

The study may be the first to link apoptosis, the gene-driven process that leads to the necessary destruction of old, damaged, or infected cells, with epigenetics — the study of how gene function changes even when the genes themselves don’t change.

Scientists believe that defects in cell death regulation may be responsible for tumor formation and the spread of cancer, because the cells escape the safeguards that normally clean up malignant cells.

In their experiments, UF researchers found the location of the DNA sequences known to trigger reaper, hid and other genes related to cell death in fruit flies. Similar genes exist in humans.

By monitoring gene activity levels and changes in chromatin — the protein spools that the genes wrap around — researchers were able to detect factors that made the cells resistant to radiation.