Proto-oncogenes are normal, healthy genes found within the cells of the body. They contain instructions for making proteins that regulate cellular activities like growth, division, and differentiation. These genes ensure cells behave in an organized and controlled manner, contributing to the balance needed for normal physiological processes.
Normal Roles in Cell Regulation
Proto-oncogenes regulate cell activities, acting like accelerators for cell division. They produce proteins that stimulate cell growth and proliferation when new cells are needed, such as during development or tissue repair.
These genes also influence the cell cycle, the series of events cells undergo as they grow and divide. Their protein products help cells move through the cycle, promoting orderly progression. Proto-oncogenes are also involved in cell differentiation, the process where cells become specialized for specific functions, such as developing into muscle or nerve cells.
The Transformation: From Proto-Oncogene to Oncogene
A proto-oncogene can transform into an oncogene, a gene promoting cancer, through specific genetic alterations. This conversion, often termed activation, results in the gene’s protein product becoming overactive or overproduced. One common mechanism is a point mutation, where a single DNA nucleotide is altered, inserted, or deleted. This subtle change can lead to a protein that is continuously “on,” constantly signaling for cell growth even when not needed.
Another way proto-oncogenes become oncogenes is through gene amplification, creating too many copies of the gene. This leads to an excessive amount of the protein, causing uncontrolled cellular activity. Chromosomal translocations also contribute, where a piece of one chromosome attaches to another. This rearrangement can place a proto-oncogene next to a strong regulatory sequence, causing abnormally high expression or creating a hyperactive fusion protein.
Oncogenes and Cancer Development
Once a proto-oncogene becomes an oncogene, its altered function directly drives uncontrolled cell growth and division, hallmarks of cancer. Acting like a “stuck gas pedal,” an oncogene continuously signals cells to multiply, leading to tumor formation. This unregulated growth disrupts the body’s normal tissue architecture.
Oncogenes interfere with cell signaling pathways, overriding natural checkpoints that regulate the cell cycle. This allows cells to bypass controls that would halt division if errors occurred. Some oncogenes also enable cancer cells to evade apoptosis, or programmed cell death, allowing abnormal cells to survive and proliferate. Certain oncogenes can also stimulate angiogenesis, the formation of new blood vessels, supplying tumors with nutrients and oxygen to grow and spread.
Common Oncogenes and Their Associated Cancers
Several well-studied proto-oncogenes are frequently found as activated oncogenes in human cancers. The RAS gene family is a common oncogene involved in approximately 20% of all human malignancies. Mutations in RAS genes are often observed in pancreatic, colon, and lung cancers, contributing to uncontrolled cell growth signals.
Another example is the MYC gene, which, when activated, can lead to lymphomas and leukemias, such as Burkitt lymphoma. MYC codes for transcription factors that regulate gene expression, and its overexpression results in excessive production of these factors, promoting cell proliferation. The HER2 gene (also known as ERBB2) is implicated in certain breast and gastric cancers. Amplification of HER2 leads to an abundance of its protein product, a receptor that promotes cell division, contributing to aggressive tumor behavior.