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| Estrogen is another chemical that can become quite toxic when combined with other chemicals present in the body. Most of these transforming activities take place in the liver. |
| Proto-oncogenes may be classified into four groups: |
| 1. Growth factors. These factors occur outside the cell and encode homologous proteins. Although they appear normal, they are not. They stimulate cell signaling, such as platelet-derived growth factors. |
| 2. Crowth-factor receptors. These act as cell receptors receiving oncogenic information. Many growth-factor receptors contain protein tyrosine kinase activity, for example, erbB-2 protein, a newly identified proto-oncogene found in some forms of aggressive breast cancer. |
| 3. Signal transducers. These are components of the intracellular signaling pathways. Signals are transmitted from cell-membrane receptors to the nucleus by second messengers. Cascades of protein kinases are involved in mediating these signals by way of proto-oncogenes. At this time, the most widely known and best understood is the ras gene. Cyclin-dependent kinases (CDKs) are a group of kinases involved in many cancers. |
| For example, CDK-1 plays an important role in the cell division of 40 percent of all cancers and an astounding 90 percent of all breast cancers. The expression of this protein facilitates the proliferation of vascular endothelial cells, which form the basis for creating blood vessels that feed hew tumors, part of the process known as angiogenesis. CDK-4, another newly identified CDK, is involved with disturbing the control of one of the cell's phases of division. Suppression of CDK-1 and other CDKs is the target of many new cancer drug therapies. Currently, CDK-1 is also being used as a marker for assessing the aggressive nature of a cancer and as a risk factor for metastatic cancer growth. |
| 4. Nuclear transcription factors. By binding to DNA in a sequence-specific manner, nuclear transcription factors activate gene expression within the nucleus of the cell. Myc, fos, and jun are three of the most well-known nuclear transcription factors. |
| Tumor-Suppressor Genes |
| Another class of cancer genes are the previously mentioned tumor-suppressor genes. Mutations that knock out tumor-suppressor genes are more threatening than the activation of oncogenes, previously thought to be the most important |
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