Protein turns pancreatic cancer cells into normal cells

In a breakthrough, scientists have shown that it is possible to coax pancreatic cancer cells to turn into normal cells by introducing a protein.
"For the first time, we have shown that overexpression of a single gene can reduce the tumour-promoting potential of pancreatic adenocarcinoma cells and reprogramme them toward their original cell type," said Pamela Itkin-Ansari, adjunct professor in the Development, Aging, and Regeneration Programme at Sanford-Burnham Medical Research Institute in US.
Pancreatic adenocarcinoma is the most common form of pancreatic cancer. It's primarily caused by a mutation in the oncogene called Kras that causes the digestive enzyme-secreting cells (acinar cells) to differentiate into a destabilised duct-like cell type, which is cancerous.

The disease is often called a "silent" cancer because it rarely shows early symptoms - it tends to be diagnosed at advanced stages when it causes weight loss, abdominal pain, and jaundice.
The new study generated human pancreatic ductal adenocarcinoma cell lines to make higher than normal levels of E47.
The protein, E47, binds to specific DNA sequences and controls genes involved in growth and differentiation.

The increased amount of E47 caused cells to stall in the growth phase, and differentiate back toward an acinar cell phenotype.
In vivo studies showed that when the reprogrammed cancer cells were introduced into mice, their ability to form tumours was greatly diminished compared to untreated adenocarcinoma cells.

"Presently, pancreatic adenocarcinoma is treated with cytotoxic agents, yet the average survival for patients post-diagnosis is merely six months, and the improvements in therapies are measured in days," said Andrew M Lowy, professor of surgery at the University of California, San Diego Moores Cancer Center.
"The finding that we can differentiate these cancer cells back to a non-threatening phenotype is encouraging.
"Indeed, there is a precedent for cell differentiation therapy in that the approach has been used to treat acute promyelocytic leukemia (APL) and some neuroblastomas successfully," Lowy said.
"Our next step is to test primary patient-derived tumour tissue to determine whether E47 can produce similar results, potentially providing a novel therapeutic approach to combat this highly lethal disease," said Itkin-Ansari.

"Additionally, we are screening for molecules - potential drugs - that can induce overexpression of E47," said Itkin-Ansari.
The study is published in the journal Pancreas.