Ras gene products are involved in kinase signaling pathways that control the transcription of genes, which then regulate cell growth and differentiation. To turn "on" the pathway, the ras protein must bind to a particular molecule (GTP) in the cell. To turn the pathway "off," the ras protein must break up the GTP molecule. Alterations in the ras gene can change the ras protein so that it is no longer able to break up and release the GTP. These changes can cause the the pathway to be stuck in the "on" position.(1) The "on" signal leads to cell growth and proliferation. Therefore, ras overexpression and amplification can lead to continuous cell proliferation, which is a major step in the development of cancer.(2) Cell division is regulated by a balance of positive and negative signals. When ras transcription is increased, an excess of the gene's protein is in the cell, and the positive signals for cell division begin to outweigh the negative signals.
The conversion of ras from a proto-oncogene into an oncogene usually occurs through a point mutation in the gene. The altered function can affect the cell in different ways because ras is involved in many signaling pathways that control cell division and cell death. Anti-cancer drugs are now being developed that target ras dependent pathways. Much remains to be discovered before these drugs can be put into use.(3)
Mutant ras has been identified in cancers of many different origins, including: pancreas (90%), colon (50%), lung (30%), thyroid (50%), bladder (6%), ovarian (15%), breast, skin, liver, kidney, and some leukemias.(1) It is also possible that in the future, ras may be used to detect certain cancers. Historically, pancreatic cancer has been difficult to diagnose. The identification of ras mutations in the DNA of pancreatic cells shed into feces may enable clinicians to differentiate between chronic pancreatitis and pancreatic cancer.(1)