Proto-oncogenes are normal genes that stimulate cell division. Many code for growth factors, or for the receptor proteins on the cell-surface membrane that bind growth factors. When a growth factor binds, the receptor triggers a series of reactions that switches on the genes needed for DNA replication and cell division. In a healthy cell, proto-oncogenes are active only when cell division is needed.An oncogene is a mutated or abnormally activated proto-oncogene. It is permanently switched on, so cells divide uncontrollably and a tumour can form. This can happen in two main ways:
• The receptor protein is permanently activated, so it triggers DNA replication and cell division even when no growth factor is present.
• The gene is over-expressed, so too much growth factor is made.A proto-oncogene can become an oncogene through:
• a mutation in its base sequence
• hypomethylation (decreased methylation), which increases its transcription.Only one allele needs to change for an oncogene to have an effect, because the abnormal protein drives cell division whatever the normal allele does. In contrast, both alleles of a tumour suppressor gene usually need to be inactivated.A useful analogy: proto-oncogenes are the accelerator of the cell cycle, and tumour suppressor genes are the brake. An oncogene is an accelerator stuck down; an inactivated tumour suppressor gene is a brake that has failed. Most cancers involve both.An example is the RAS gene, which codes for a protein in the growth factor signalling pathway. Mutated RAS is found in many cancers.
• The receptor protein is permanently activated, so it triggers DNA replication and cell division even when no growth factor is present.
• The gene is over-expressed, so too much growth factor is made.A proto-oncogene can become an oncogene through:
• a mutation in its base sequence
• hypomethylation (decreased methylation), which increases its transcription.Only one allele needs to change for an oncogene to have an effect, because the abnormal protein drives cell division whatever the normal allele does. In contrast, both alleles of a tumour suppressor gene usually need to be inactivated.A useful analogy: proto-oncogenes are the accelerator of the cell cycle, and tumour suppressor genes are the brake. An oncogene is an accelerator stuck down; an inactivated tumour suppressor gene is a brake that has failed. Most cancers involve both.An example is the RAS gene, which codes for a protein in the growth factor signalling pathway. Mutated RAS is found in many cancers.