Cancer

• Healthy cell

  • Rest
  • Grow
  • Divide
  • Differentiate
  • Die
• Cancerous cells divide repeatedly out of control even though they are not needed, they crowd out other normal cells and function abnormally
• Cancer cells:

  • small cytoplasm
  • multiple nuclei
  • multiple and large nucleoli
  • coarse chromatin
• Cancer has

  1. unlimited growth: turn on growth promoter genes
  2. ignore checkpoints: turn off tumor suppressor genes (p53)
  3. evade apoptosis: turn off suicide genes
  4. unlimited divisions: turn on chromosome maintenance genes
  5. promotes blood vessel growth: turn on blood vessel growth genes
• Cancer is essentially a failure of cell division control
• What control is lost?

  • lose checkpoint stops
  • gene p53 plays a key role in G1/S restriction point
• Replicative senescence

  • process by which normal somatic cells reach an irreversible stage of cell cycle arrest following multiple rounds of replication; this end stage is associated with marked changes in gene expression and function.
• p53 protein halts cell division if it detects damaged DNA
• All cancers have to shut down p53 activity
• “Go-ahead” signals

  • Primary mechanism of control is through phosphorylation
  • kinase enzymes either activates or inactivates cell signals
• proto-oncogenesnormally activates cell

  division

  • growth factor genes

  become oncogenes

  (cancer-causing)

  when mutated
• proto-oncogenes

  • normally activates cell division
  • growth factor genes become oncogenes (cancer-causing) when mutated
• Gain of function mutations creates oncogenes
• In cells that have become cancerous, apoptosis does not occur
• Cancerous cells can trick cell to skip apoptosis with the inactivation of p53. Cancer can produce BcL-2 or protein which mimics Bcl-2 (inhibits apoptosis)
• Inhibit expression of the gene for Apaf-1. Blocks the T-cells’ FasL, or kill cytotoxic T cells with FasL.
• Metastatis: Invasion/migration into new tissues, establishing secondary areas of proliferation
• Tumor: Mass of abnormal cells
• Benign tumor: abnormal cells remain at original site as a lump , hold together by cell adhesion molecules. Most do not cause serious problems & can be removed by surgery.
• Malignant tumor (cancer)

  • cells leave original site
  • lose attachment to nearby cells
  • carried by blood & lymph system to other tissues
  • start more tumors = metastasis
  • impair functions of organs throughout body
• Metastasis

  • To metastasize the cell must alter its cell adhesion molecules and degrade the extracellular matrix and basal lamina (epithelial-to-mesenchymal transition)
• MMP and plasminogen activator are some of the proteins secreted by cancer cells to degrade the ECM
• Angiogenesis

  • Tumor growth requires formation of new blood vessels
• Neovascularization: makes rapid tumor growth possible by supplying oxygen and nutrients and removing waste and facilitating metastasis
• Growth factors (angiogenic properties)

  1. Basic fibroblast growth factor
  2. Transforming growth factorα
  3. Vascular endothelial growth factor (VEGF)
• Cancer has altered metabolism

  • Increased glucose uptake and preferential production of lactate, even in the presence of oxygen (called Warburg effect)
  • Lifestyle plays a role in cancer prevention