Lecture Notes: Oncogene Activation and Tumor Suppressor Deactivation in Cancer

Key Concepts

• Proto-oncogenes and Tumor Suppressor Genes
  • Proto-oncogenes: Normal genes that promote cell cycle progression and division.
    • Controlled expression is crucial.
    • Mutation can activate them into oncogenes, leading to gain-of-function.
  • Tumor Suppressor Genes: Inhibit cell cycle progression, promote cell death, and repair DNA.
    • Loss of function through mutation can lead to cancer.

Oncogene Activation

• Proto-oncogenes to Oncogenes
  • Proto-oncogenes are the unmutated form.
  • Oncogene activation involves loss of control, turning them into oncogenes.
  • Gain-of-function mutation results in uncontrolled cell growth.
• Types of Mutations
  • Point mutations.
  • Chromosomal rearrangements.
  • Gene amplification (e.g., HER2 in breast cancer).
  • Oncogenes are dominant, requiring a single mutation to cause effects.
• Analogy
  • Proto-oncogenes as car accelerators: Necessary for movement but dangerous if stuck.

Tumor Suppressor Deactivation

• Role of Tumor Suppressor Genes
  • Halt cell cycle, ensure DNA repair, and induce cell death when necessary.
  • Loss of function can result in unchecked cell growth.
• Types of Deactivation
  • Deletions.
  • Point mutations.
  • Epigenetic silencing (e.g., promoter methylation).
• Analogy
  • Tumor suppressor genes as car brakes: Vital for stopping, and loss leads to loss of control.

Cancer Development

• Process
  • Mutations accumulate, providing growth advantages to cells.
  • Can involve both oncogene activation and tumor suppressor loss.
• Carcinomas
  • Most common cancers originate in epithelial layers (e.g., ductal carcinoma in the breast).
  • Invasive and metastatic potential increases with mutation accumulation.

Genetic Classification

• Oncogenes
  • Promote cell survival/proliferation; dominant mutations.
  • Examples include anti-apoptotic factors, growth factor receptors.
• Tumor Suppressor Genes
  • Inhibit survival/proliferation; recessive mutations requiring two hits.
  • Include apoptosis promoters and cell cycle inhibitors.

Clinical Implications

• HER2 and Breast Cancer
  • HER2 gene amplification leads to overexpression of growth factor receptors.
  • Clinical diagnosis involves detecting gene amplification through cellular imaging.

Conclusion

• Understanding proto-oncogenes and tumor suppressor genes is key to understanding cancer mechanisms.
• Mutations in these genes lead to excessive survival and proliferation, forming the basis of many cancers.