PCB 3023 - Chapter 20: Cancer Review Notes

Cell Cycle Differences in Cancer Cells

  • Cancer cells divide uncontrollably.
  • They ignore signals to stop dividing.
  • They bypass checkpoints that normally prevent division with damaged DNA.

Distinguishing Features of Cancer Cells

  1. Reduced dependence on external signals.
  2. Less prone to apoptosis (programmed cell death).
  3. Proliferates indefinitely.
  4. Genetically unstable.
  5. Invasive, capable of penetrating surrounding tissues.
  6. Able to survive in foreign tissues.

Metastasis

  • Metastasis is the spread of cancer cells from the primary tumor site to form secondary tumors in other parts of the body.

Benign vs. Malignant Tumors

  • Benign Tumors:
    • Proliferate despite normal constraints.
    • Remain clustered in a single mass.
    • Can usually be removed cleanly by surgery.
  • Malignant Tumors (Cancerous):
    • Proliferate excessively.
    • Invade and colonize other tissues.
    • Can spread via blood or lymph.
    • Form secondary tumors.
  • The transition from benign to malignant is considered a single stage.

Cancer as a Genetic Disease

  • Cancer is considered a genetic disease because it arises from pathological changes in DNA.
  • Difference from Sickle Cell Anemia: Cancer is characterized by uncontrolled cell growth and division, while sickle cell anemia is a genetic disorder affecting red blood cell shape and function.

Function of Proto-oncogenes and Tumor Suppressor Genes

  • Proto-oncogenes (Normal Function):
    • Involved in cell division and survival.
  • Proto-oncogenes (Mutated):
    • Become oncogenes when overactive, leading to tumors.
  • Tumor Suppressor Genes (Normal Function):
    • Block cell division and prevent tumor formation.
  • Tumor Suppressor Genes (Mutated):
    • Become underactive, leading to tumor formation.

Mutations in Proto-oncogenes vs. Tumor Suppressor Genes

  • Proto-oncogenes:
    • Only one mutated copy is needed to cause an effect (dominant mutation).
    • The mutation results in a gain of function.
  • Tumor Suppressor Genes:
    • Both copies need to be mutated to lose function (recessive mutation).
    • If only one copy is inactivated, the other can still function.

Examples of Proteins from Proto-oncogenes and Tumor Suppressor Genes

  • Proto-oncogenes:
    • RTK (Receptor Tyrosine Kinase) which activates Ras, which then activates the MAP kinase cascade.
    • Bcl-2 (anti-apoptotic protein).
  • Tumor Suppressor Genes:
    • Rb (Retinoblastoma protein).
    • p53 (Tumor protein p53).
    • APC (Adenomatous Polyposis Coli).

Signal Transduction and Runaway Cell Cycle

  • Besides overproduction of growth factors, alterations in cell proliferation (e.g., mitogens) and cell survival (e.g., survival factors) can lead to an uncontrolled cell cycle.

p53 Response to DNA Damage

  • Minimal DNA Damage:
    • p53 activates a cell cycle arrest to allow time for DNA repair.
  • Irreparable DNA Damage:
    • p53 triggers apoptosis to eliminate the compromised cell.

Rb Protein Function

  • Rb normally prevents a cell from progressing through the cell cycle by binding to transcription factors.
  • In the absence of Rb, transcription factors bind to DNA, activating genes that cause the cell to proliferate.

Altered Functions in Cancer Cells

  • Cell Proliferation (Division):
    • Significantly enhanced, leading to uncontrolled division.
    • Telomerase reactivation can contribute to cancer.
  • Apoptosis (Programmed Cell Death):
    • Often impaired, preventing elimination of damaged cells.
  • Cell Adhesion:
    • Frequently altered, allowing cells to detach and migrate.
    • Cancer cells downregulate cell adhesion molecules (e.g., E-cadherin), facilitating detachment and migration.

Tumor Evolution

  • Tumors evolve through repeated rounds of mutation, proliferation, and natural selection. Mutations that provide a growth or survival advantage are retained and passed on.