By Shirley Skeel
TACOMA – Professor Leslie Saucedo has published research that casts a surprising new light on the role played by a protein associated with many forms of cancer. The study—co-researched with five University of Puget Sound biology students and alumni—reveals that the protein may have a therapeutic, rather than detrimental, role at certain stages of cancer growths.
The genetic research was published in PLOS ONE, an international, peer-reviewed, online publication that reports on primary research from many disciplines. Saucedo, associate professor of biology, was supported by a $200,000 grant from the National Institutes of Health and National Cancer Institute awarded in 2009. She initiated the research while at the Fred Hutchison Cancer Research Center in Seattle.
The student and alumni co-writers of the paper, “Drosophila PRL-1 is a Growth Inhibitor That Counteracts the Function of the Src Oncogene,” include Krystle Pagarigan ’11, Bryce Bunn ’13, Jake Goodchild ’04, Travis Rahe ’11, and Julie Weis ’08. Peer reviewers said that the research offers a good system to start understanding the protein PRL in normal cells and expressed interest in seeing further work. The paper has had more than 500 page views just two weeks after going online.
The new findings indicate that the protein PRL, which occurs at abnormally-high levels in human cancers, can actually slow cell growth and counter the formation of cancer tumors in the common fruit fly Drosophila melanogaster. Past studies had suggested the opposite—that high levels of PRL contribute to the progression of cancer. Those studies, however, took place using human or mouse cells that were already cancerous or growing abnormally. This new report is the first to examine PRL activity in normal cells in a living organism.
Importantly the new results suggest that PRL may, at a certain time, be “flipped” from suppressing tumors to adversely advancing the cancerous growth. The authors say this could be due to some other genetic or environmental change in the cells.
“This work establishes a new system that has revealed novel characteristics of PRL and that will help decipher the role or roles that PRL play in cancers,” Saucedo said.
On her Web page Saucedo remarks about the current work: “We appear to be the only fly lab investigating PRL-1 and I see us in a prime position to significantly inform the field of human cancer biology.”
Saucedo says the fruit fly research could also apply to humans, because many experiments with Drosophila have revealed cancer mechanisms that also contribute to human cancer. The findings could prove to be relevant to many kinds of cancer. High levels of PRL have been reported as a cancer marker in colon, liver, gastric, breast, ovarian, cervical, rectal, and nose and throat cancers.
This summer Saucedo and her students will continue the work on PRL. They will put human PRL into flies to see if there is a different outcome. They will also genetically remove PRL from flies to determine where and when the protein is needed in the insect’s development. This may throw light on why cancer cells may “take advantage” of it.
In addition the team has a hypothesis about just what could be serving as the switch that makes PRL either counter or contribute to cancers. They will genetically engineer a modified PRL to test the theory. Saucedo will be applying for a research grant from the M.J. Murdock Charitable Trust to support the work.