Another piece of the puzzle

Professors and students discover gene associated with breast cancer

RADNOR » While it’s basic research at the moment, the discovery of a gene’s link to breast cancer by a Villanova University team may lead to a better understanding of that lethal disease.

Janice Knepper, Ph.D., a professor at Villanova University, and her students, have been studying the ZC3H8 gene, known as Fliz1, for the last eight years. Their findings were recently published in BMC Cancer, a medical journal.

“It’s a piece of ongoing work that’s been in the pipeline for quite a few years,” said Knepper.

“It’s grown out of a project I’ve been working on for quite a long time trying to identify genes associated with tumors in mice.”

Knepper characterized the research, done with mice, as “basic.”

“We have not explored, in depth, any human effects,” she said.

However, the activity of the gene appears to make tumors more aggressive.

“We’ve been looking for genes that are involved in breast cancer in the mouse and identified this one as being abnormally highly productive in a number of mouse tumors,” she said. “A higher expression of this gene is associated with a poorer prognosis in some human tumors.”

“We don’t know that there’s any association with human cancer, but the mouse is a good model for human cancer and genes that have been studied in the past also have been shown to have a similar function in humans,” Knepper said.

Several of Knepper’s students are named as coauthors on the research, along with her colleagues, John Schmidt, Ph.D., the lead author, and her husband, Keith Danielson, Ph.D. All five of the student authors are currently doing postgraduate studies in science or medicine, she said.

Knepper, of Bryn Mawr, grew up near Baltimore, attended Mount Holyoke College and earned her doctorate from Brown University. She also did post-doctoral work at Johns Hopkins University and Baylor College of Medicine.

Knepper planned to major in math in college before a teacher wrote in her yearbook that she should major in biology.

Knepper, the co-director of the program in biochemistry at VU, said that she “wanted to understand how living cells worked mechanistically, why certain actions take place in cells as a result of the genes that are expressed. So I wanted to know how that worked. It’s more rewarding to work on a project that has some implications for public benefit.”

“It’s not applied research,” said Knepper. “It’s basic research. You have to understand what’s going in the basic level to target a drug.

“We used mouse cells in culture, and these cells have derived from a common laboratory strain of white mice,” Knepper explained. “We can grow them in vitro, but because they are from this inbred strain of mice, we can put the cells back into the mice and look at their tumorforming ability.”

The mice accept those cells because they have the same genetic background, she said.

“That allows us to draw parallels between the cells’ behavior in culture and their ability to form tumors in the animal,” she said.

Of more than 200,000 genes in the human body, 70 are now used to assess prognosis in breast cancer, she said.

Cancer is the secondleading cause of death in the U.S. after heart disease, according to the Centers for Disease Control, and one of every four deaths is due to cancer. In 2015, there were 242,476 new cases of female breast cancer, according to the CDC, and 41,523 women died of the disease.

SUBMITTED PHOTO Villanova biology Professor Janice Knepper is working with a team at the university to study the ZC3H8 gene, known as Fliz1. Their findings were recently published in BMC Cancer, a medical journal.