OREGON STATE UNIVERSITY

Findings may lead to new cancer therapies

02/12/2009

CORVALLIS, Ore. – Pharmacy researchers at Oregon State University have identified a protein that’s essential to life but, when “expressed” at too high a level in cells, can lead to their death.

The findings could lead to new approaches to cancer chemotherapy, the creation of assays to identify cancer, or improving the effectiveness of existing cancer drugs, scientists say.

The research was recently published in the Journal of Biological Chemistry, based on studies of COUP-TF1, a member of the super-family of steroid hormone receptors that are part of a cellular communication process.

“Like all steroid hormone and related receptors, COUP-TF1 regulates gene expression, and in this case it regulates one of the genes that help control cell death,” said Mark Leid, a professor and assistant dean of the OSU College of Pharmacy. “Cells die and are replaced all the time, this is a natural process. What we found was that production of too much of this protein can lead to early, induced cell death.”

One of the most basic approaches to cancer therapy is to find ways – through radiation or chemotherapeutic drugs – to kill cancer cells without damaging normal cells. It may be possible, Leid said, to induce cancer cells to overproduce COUP-TF1 and cause their death – some drugs are already available that are known to elevate levels of the COUP-TF1 protein.

This could form a basis for new types of chemotherapy, he said, or might also be used to improve the effectiveness and selectivity of existing chemotherapy drugs, and reduce their unwanted side effects.

“In the near term, we may also be able to develop assays and biomarkers that improve breast cancer therapy,” Leid said. “This should be very possible, because some breast cancers already overproduce COUP-TF1.”

This research was done in collaboration with the Fred Hutchinson Cancer Research Center in Seattle.