PITTSBURGH, April 13 -- A research team at the University of Pittsburgh Cancer Institute and Magee-Womens Hospital has uncovered a pivotal role for problems with DNA repair in breast cancer, which could help explain why most early-stage breast cancers respond to available treatments and why advanced tumors thrive despite aggressive therapy. The report provides the first evidence that cells from early-stage breast cancers fail to repair DNA like normal cells through nucleotide excision repair (NER). The details will be reported at a scientific minisymposium on April 13 at the annual meeting of the American Association for Cancer Research in Philadelphia.
To begin, the research team looked at the level of mutations in a marker gene often used to indicate exposure to DNA-damaging agents. They found significantly elevated levels of mutations in this marker gene in newly diagnosed breast cancer patients compared with levels in controls, suggesting a problem with DNA repair in women with the disease. Next, they studied the activity of NER enzymes in various tissues from these women.
"We found that NER activity is substantially reduced in breast cancers taken from patients with ductal carcinoma in situ, stage I or stage II cancers," explained Jean Latimer, Ph.D., assistant professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh and investigator at the Magee-Womens Research Institute. "We found a reduction in NER activity in every breast cancer patient tissue we examined but in no control breast tissue samples taken from women undergoing routine breast reduction surgery," she added.
About 30 different NER proteins are necessary to detect and repair injuries from
ultraviolet radiation, x-rays and chemical toxins. Like linemen who inspect
each railroad tie along a set of tracks before a train passes over them, NER
enzymes inspect each nucleotide of a DNA helix for any damage before another set
of enzymes encounters
Contact: Lauren Ward
University of Pittsburgh Medical Center