Introduction
Cancer is a genetic disease caused by mutations that alter the regulation of cell growth and division. Two major types of genes involved in the development of cancer are proto-oncogenes and tumor suppressor genes. When these genes are altered, they disrupt the normal control of cell cycle, leading to uncontrolled cell growth — the hallmark of cancer.
Proto-oncogenes and Their Role
Proto-oncogenes are normal genes that encode proteins involved in cell growth, division, and survival. When these genes undergo mutation or become overexpressed, they convert into oncogenes, which promote cancerous growth.
Functions of Proto-oncogenes:
- Stimulate cell division
- Promote cell survival
- Participate in signal transduction pathways
Mechanism of Cancer Development:
Mutations in proto-oncogenes lead to continuous cell division even in the absence of growth signals. These gain-of-function mutations cause the gene to be constantly active.
Examples of Proto-oncogenes:
- RAS gene: Encodes a GTPase involved in cell signaling. Mutated RAS remains permanently active, promoting cell proliferation in cancers like pancreatic, colon, and lung cancer.
- HER2 (Human Epidermal growth factor Receptor 2): Overexpression is associated with aggressive breast cancers.
Tumor Suppressor Genes and Their Role
Tumor suppressor genes are genes that normally inhibit cell division, promote DNA repair, and trigger apoptosis (programmed cell death). When these genes are inactivated due to mutations, cells can grow uncontrollably.
Functions of Tumor Suppressor Genes:
- Regulate cell cycle checkpoints
- Repair damaged DNA
- Initiate apoptosis when necessary
Mechanism of Cancer Development:
Loss-of-function mutations in both copies of a tumor suppressor gene (known as the “two-hit hypothesis”) remove the cell’s ability to regulate growth and division, allowing mutated cells to survive and proliferate.
Examples of Tumor Suppressor Genes:
- TP53 gene: Known as the “guardian of the genome,” it encodes the p53 protein that arrests the cell cycle in response to DNA damage. Mutations in TP53 are found in over 50% of all human cancers.
- RB1 gene: Responsible for the regulation of the G1 to S phase of the cell cycle. Its mutation leads to retinoblastoma, a rare eye cancer in children.
Key Differences Between Proto-oncogenes and Tumor Suppressor Genes
| Feature | Proto-oncogenes | Tumor Suppressor Genes |
|---|---|---|
| Normal Function | Promote cell growth and division | Inhibit cell growth and promote repair/apoptosis |
| Mutation Effect | Gain of function (activation) | Loss of function (inactivation) |
| Mutation in One or Both Alleles | Only one allele needs to be mutated | Both alleles must be inactivated |
Conclusion
The interplay between proto-oncogenes and tumor suppressor genes maintains the delicate balance of cell growth and death. Disruption of this balance leads to tumor development. Understanding their role in cancer formation has led to the development of targeted therapies and diagnostic tools, significantly improving cancer treatment and prognosis.