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Types of Proto-Oncogenes

A proto-oncogene is a normal gene that can cause cancer if the gene becomes mutated or if regulation of its expression goes awry. Genes classified as proto-oncogenes are found in all cells, and they usually play roles in the cell cycle and in cell growth and differentiation. Mutations and overexpression of proto-oncogenes can lead to tumor growth and metastasis.

  1. Growth Factors

    • Growth factors are protein molecules that bind receptors on the cell membrane and trigger a signaling cascade that leads to increased cell division and proliferation. Many of the genes that code for growth factors are proto-oncogenes. Normal expression of these genes can be triggered by growth or response to injury. But when growth factor genes are expressed at unusually high levels that cannot be turned off, cancer can result. SIS and int-2 are examples of proto-oncogenes that are growth factors.

    Membrane Receptors

    • Protein receptors on the cell membrane, especially those that receive signals from growth factors, can also be proto-oncogenes. In normal situations, receptor proteins' responses to growth signals are limited and well regulated. If a gene involved in the signaling chain for a receptor protein becomes mutated, the receptor protein might fail to respond to termination signals, and uncontrolled growth and tumor development can result.

    Transcription Factors

    • Genes that code for transcription factors are also frequently proto-oncogenes. Transcription factors are molecules in the cell's nucleus that bind DNA and induce transcription upon receiving a signal, such as that of a hormone. If the genes encoding transcription factors are able to proceed without normal regulation, they can become oncogenes, and cancer can result. The MYC genes are an example of transcription factor genes that are considered proto-oncogenes.

    Cyclins

    • Cyclins are proteins that regulate the cell cycle, together with cyclin-dependent kinases. Because cancer always involves cell cycle disturbances, such as uncontrolled cell division with failure to halt in response to DNA damage, mutations in the genes that code for cyclins have definite cancer-causing potential. Cyclin D1, for example, regulates when the cell moves from the G1 (first growth) phase to S (DNA synthesis) phase, and the gene for cyclin D1 is often found to be mutated in certain types of cancer.

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