Chapter 6 : On the Origin of Oncogenes

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This chapter first reviews Howard Temin's thoughts on the origin of cancer genes, who had correctly predicted many aspects of the current understanding of the molecular alterations responsible for the development of malignant tumors. The chapter discusses some of the functions of proto-oncogenes in controlling normal cell growth and differentiation as well as the possibility that oncogene proteins provide novel targets for cancer chemotherapy-areas of current interest which represent direct outgrowths of some of Howard's seminal contributions to cancer research. All three key elements of Howard's hypothesis for the origin of cancer genes have proven correct. First, mutations play a critical role in converting protooncogenes to oncogenes as well as in inactivating tumor suppressor genes. Second, similar oncogenes are found in both strongly transforming retroviruses and nonvirus-induced tumors, including human cancers. Third, reverse transcription is involved in at least some mutations of proto-oncogenes and tumor suppressor genes in non-virus-induced tumors as well as being responsible for the incorporation of oncogenes into retroviral genomes. The discovery that oncogenes are mutated versions of normal cell genes (proto-oncogenes) focused attention on the roles of proto-oncogenes in normal cells and on the nature of the molecular alterations that convert proto-oncogenes to oncogenes. The chapter concludes with a brief consideration of the possibility that oncogenes provide novel targets against which drugs with increased selectivity for cancer cells could be designed. Posttranslational modification of Ras proteins by addition of a farnesyl isoprenoid is required for their membrane association and biological activity.

Citation: Cooper G. 1995. On the Origin of Oncogenes, p 63-80. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch6

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Figure 1

Ras proteins in mitogenic signal transduction. Ras proteins are activated downstream of receptor protein-tyrosine kinases. The Raf protein-serine/threonine kinase then binds to Ras, which serves to recruit Raf to the plasma membrane. Activated Raf then phosphorylates and activates MEK, which in turn phosphorylates and activates MAP kinase (MAPK).

Citation: Cooper G. 1995. On the Origin of Oncogenes, p 63-80. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch6
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Figure 2

Distinct pathways signal differentiation and survival of PC12 cells in response to NGF.

Citation: Cooper G. 1995. On the Origin of Oncogenes, p 63-80. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch6
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Table 1

Examples of oncogenes in human cancers

Citation: Cooper G. 1995. On the Origin of Oncogenes, p 63-80. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch6
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Table 2

Tumor suppressor genes

Citation: Cooper G. 1995. On the Origin of Oncogenes, p 63-80. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch6
Generic image for table
Table 3

Functions of representative proto-oncogenes

PDGF, platelet-derived growth factor; FGF, fibroblast growth factor; EGF, epidermal growth factor; IL-2, interleukin 2.

Citation: Cooper G. 1995. On the Origin of Oncogenes, p 63-80. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch6

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