A novel tumor suppressor identified by researchers at the University of Cincinnati (UC) has given a new thrust to lung cancer management.
Proto-oncogenes are genes that play a role in normal cell growth (turnover of cells and tissue) but, when genetically modified, can cause the out-of-control cell division that leads to cancer.
AdvertisementPrevious research had established that Ras, a proto-oncogene, is abnormally expressed in up to 25 percent of human lung cancers; but, researchers did not understand the specific cellular events by which abnormal Ras expression leads to transformation.
The research team, led by Jorge Moscat, sought to define the interim steps that occur in Ras-induced tumour development to better understand the underlying biological mechanisms leading to cancer.
"These interim steps are critical because they help us determine how best to intervene and stop cancer growth along the way. Right now, cancer therapy is delivered with a sledgehammer and it needs to be more like a scalpel so we avoid unnecessary harm to the body," said Moscat, co-author of the study and chair of UC's cancer and cell biology department.
Using a genetically modified mouse model, the researchers found that animals that didn't express a certain gene (protein kinase C (PKC)-zeta) developed more Ras-induced lung cancer, suggesting a new role for the gene as a tumour suppressor.
"PKC-zeta would normally slow down Ras transformation and put the brakes on tumour development, but when PKC-zeta is missing or inactive as a result of genetic alterations, tumour growth actually accelerates," said Moscat.
"Until now, we did not know the specific chain of events that led to Ras-induced lung cancer. Our study fills in important missing information that will enhance our overall understanding of how lung cancer tumours grow and spread," Moscat added.
The study appears in the January 2009 issue of Molecular and Cellular Biology.