Oncogene

Aka: Oncogene, Proto-oncogene, Retroviral Oncogene

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II. Definitions

  1. Oncogene
    1. Gene that is normally involved in cell growth, but now mutated, and allowing for uncontrolled cancer growth
    2. Oncogenes may be inherited, or acquired from environmental exposures (viruses, substances)
    3. Oncogenes prefixed by -v, indicate a Retroviral Oncogene
  2. Proto-oncogene
    1. Proto-oncogene is a gene normally involved in cell growth regulation
    2. Proto-oncogenes may mutate into Oncogenes and lead to the uncontrolled growth of cancer cells
    3. Proto-oncogenes include cell proliferation stimulators (mitogens)
      1. Growth factors (e.g. EGF, PDGF)
      2. Protein kinases
      3. Signal transducers
      4. Nuclear phosphoproteins
      5. Transcription factors
  3. Retroviral Oncogene of Acute Transforming Viruses
    1. Retrovirus (e.g. HTLV) transmits Oncogenes to host cells
    2. Retroviral Oncogenes are associated with Sarcomas and Leukemias
    3. First identified in birds and rodents

III. Pathophysiology: Mechanisms of Oncogene transmission

  1. Acute Transforming Viruses
    1. Retrovirus (e.g. HTLV) transmits an intact Oncogene from its genome to host DNA
      1. Oncongenes have sticky ends (single stranded overhanging DNA)
      2. Retroviruses express an integrase enzyme that facilitates the Oncogene integration
    2. Viruses may "capture" Proto-oncogenes from hosts into their own genomes
      1. Captured Proto-oncogenes may mutate over time with viral replication into Oncogenes
  2. Defective Acute Transforming Viruses
    1. Most acute transforming viruses are defective and rely on viral coinfection for replication
      1. Oncogenes are very long RNA Nucleotide sequences
      2. Acute transforming viruses with long Oncogenes lose the RNA needed for viral replication
    2. Rous Sarcoma virus Oncogene (src) is an exception and is not defective
      1. Src maintains a full Oncogene and its own viral replication RNA
  3. Non-acute transforming viruses
    1. Retrovirus carries RNA coding for an activating sequence (instead of an intact Oncogene)
    2. Activating sequence integrates into a Proto-oncogene, transforming it into an Oncogene

IV. Types: Retroviral Oncogene Examples

  1. Rous Sarcoma virus Oncogene (src)
    1. Src phosphorylates tryrosine (a signaling Protein) at 10x normal rate, stimulating unchecked cell growth
    2. Src is the first identified Oncogene, discovered in 1911 by Peyton Rous
      1. Rous transmitted Sarcoma between chickens via injection of cell-less fluid
  2. Avian Erythroblastosis virus Oncogenes (erbB, erbA)
    1. ErbB mimics receptor Tyrosine Kinase
    2. ErbA acts as a Thyroid Hormone receptor
  3. Avian Sarcoma Virus Oncogenes (16, 17, CT10)
    1. Crk (modular signaling link, CT10)
    2. Jun (AP1 transcriptional regulator, ASV17)
    3. P13K Lipid kinase (ASV16)

V. References

  1. Gladwin, Trattler and Mahan (2014) Clinical Microbiology, Medmaster, Fl, p. 266-7
  2. Vogt (2012) Nat Rev Cancer 12(9):639-48 +PMID: 22898541 [PubMed]

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