A single skin cell can become cancerous when it begins to divide uncontrollably, leading to a tumor and potentially cancer.
Genetic Basis of Cancer
Genome Composition
Humans have 23 pairs of chromosomes; half are inherited from each parent.
Two critical types of genes related to cancer: proto-oncogenes and tumor suppressor genes.
Proto-Oncogenes
Function
Encode proteins that promote the cell cycle.
Normal function involves binding growth factors, activating signal transduction, and turning on cell cycle-promoting genes.
Mutation Effects
Mutated proto-oncogenes become oncogenes, creating proteins that constantly promote the cell cycle.
Leads to constant cell division, contributing to cancer.
Only one mutated copy is needed for this effect (one-hit hypothesis).
Example Mechanism
A growth factor binds to a receptor, activating a signal cascade that promotes division.
Mutation can lead to a faulty receptor that is always "on" without growth factor binding, leading to constant division.
Tumor Suppressor Genes
Function
Create proteins that prevent cell division, acting as a check on the cell cycle.
Famous example: p53, a transcription factor that activates genes to inhibit the cell cycle.
Mutation Effects
Mutations lead to inactivation of these genes, allowing uncontrolled cell division.
Both copies need to be mutated for this effect (two-hit hypothesis).
Example Mechanism
p53 activates genes (e.g., P21) that inhibit cyclin-dependent kinases, blocking the cell cycle.
If mutated, these pathways fail, allowing division despite DNA damage.
p53 and DNA Damage
Role of p53
Activated by DNA damage to halt the cell cycle.
Prevents replication of damaged DNA, reducing cancer risk.
Mutation Consequences
If p53 is mutated in both copies, it fails to activate, allowing division even with DNA damage.
Leads to proliferation of damaged DNA and increased cancer risk.
Hypotheses Summary
One-Hit Hypothesis
Proto-oncogenes only need one mutated copy for cancerous potential.
Two-Hit Hypothesis
Tumor suppressor genes require mutations in both copies to lose function and promote cancer.
Conclusion
Understanding the genetic mechanisms of proto-oncogenes and tumor suppressor genes provides insights into cancer development and potential therapeutic targets.