Chapter 18 Genetics of Cancer


Fig. 18.7 Features of LTRs



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Fig. 18.7 Features of LTRs

  • Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
  • 6. Nononcogenic retroviruses include HIV-1, a virus that causes AIDS, rather than cancer.
    • a. The bullet-shaped capsid is surrounded by an envelope containing viral gp120 glycoproteins.
    • b. The genome contains gag, pol and env genes, and several other genes used for gene regulation (e.g., tat regulates gag and pol expression).
    • c. Infection begins when the gp120 glycoprotein in the HIV-1 envelope binds:
      • i. Most commonly, the CD4 receptor of a helper T cell.
      • ii. A different receptor on a different type of cell (e.g., macrophage, glial cell in brain, regulatory cell of intestinal lining).
    • d. The virus particle enters the cell, the protein capsid is lost and the viral life cycle begins.
    • e. Normal viral replication causes death of cells infected with HIV-1, depleting the helper T cells needed to mount an immune response. Unable to combat infection, AIDS patients frequently die of infections and cancers.
  • 7. Retroviruses that carry an oncogene (v-onc) are transducing retroviruses. Different types of cancer are caused by different v-onc genes (e.g., the sarcoma gene, v-src, of RSV).
    • a. RSV-infected cells rapidly transform, and also produce progeny RSV particles, because RSV is unusual in having intact gag, pol, and env genes.
    • b. All other transducing retroviruses are defective, lacking one or more genes needed to replicate. If a helper virus supplies the missing gene product(s), progeny can be made.

Fig. 18.8 Life cycle of a nononcogenic retrovirus

  • Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.

Fig. 18.9 Structures of four defective transducing viruses (not to scale)

  • Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
  • 8. Cellular proto-oncogenes with close homology to v-onc genes were described by Bishop and Varmus (1970s). Later work by other researchers showed that:
    • a. Oncogenes are present in human tumor cells, and cause transformation when introduced into normal cultured cells.
    • b. Human cells have genes (proto-oncogenes) that are very similar to v-onc genes, but do not induce cancers.
    • c. Proto-oncogenes are normal cellular genes that regulate cell division and differentiation.
    • d. Normal cells can become transformed without a tumor virus, if the proto-oncogene mutates to form a cellular oncogene (c-onc).
    • e. Proto-oncogenes contain introns that are missing in the corresponding v-onc.

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