Proto-oncogenes are healthy genes within cells that play a fundamental role in normal cellular processes. They contain instructions for producing proteins that regulate cell life. Their proper function is integral to the development and maintenance of healthy tissues and organs.
Normal Role of Proto-Oncogenes
Proto-oncogenes regulate cell growth and division. They produce proteins that stimulate cell division, creating new cells. These proteins also inhibit cell differentiation, where cells change to perform specialized functions.
These genes also prevent apoptosis, the body’s natural process of programmed cell death. All these functions are meticulously controlled, ensuring cells grow and divide only when necessary and in a regulated manner. This balanced activity prevents uncontrolled cellular expansion.
Transformation to Oncogenes
A proto-oncogene can transform into an oncogene, a gene with the potential to cause cancer, through genetic alterations. One common mechanism is a point mutation, a small change in the gene’s DNA sequence. Such a mutation can alter the protein, causing it to become overactive or constantly “on.”
Another way is gene amplification, where a cell acquires extra gene copies. This leads to an excessive amount of the protein, overwhelming normal regulatory mechanisms. Chromosomal translocation is a third mechanism, involving the rearrangement of chromosome segments. This can place a proto-oncogene next to a highly active promoter, leading to continuous activation, or create a fusion gene producing an abnormal, hyperactive protein.
Oncogenes and Cancer Progression
Once a proto-oncogene becomes an oncogene, its altered function contributes to cancer progression. Activated oncogenes drive uncontrolled cell division, causing cells to proliferate excessively. This bypasses normal cellular checkpoints, allowing damaged or abnormal cells to multiply.
Oncogenes also promote cell survival by interfering with apoptosis, preventing cells that should be eliminated from undergoing programmed death. This leads to an accumulation of abnormal cells, forming tumors. The sustained proliferation and survival can also enable cells to acquire further mutations, leading to the ability to invade surrounding tissues and spread to distant parts of the body, a process known as metastasis.
Key Proto-Oncogenes in Human Cancers
Several proto-oncogenes are frequently implicated in human cancers when activated. For instance, the RAS gene family plays a role in cell signaling pathways that control cell growth and division. Mutations in RAS are commonly found in pancreatic, colon, and lung cancers, leading to continuously active signaling that promotes uncontrolled cell proliferation.
HER2, a gene encoding a growth factor receptor, can become amplified in certain cancers, such as breast cancers. This amplification results in an overabundance of HER2 receptors, leading to excessive signaling for cell growth and division. The MYC gene, a transcription factor involved in regulating gene expression, is another example. MYC can be amplified or translocated, as seen in some lymphomas, driving aggressive cell growth.