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  1. Growth factors
    1. Growth factors, or mitogens, are usually secreted by a few specialized cells to induce cell proliferation in paracrine, autocrine, or endocrine manner.
    2. If a cell that usually does not produce growth factors suddenly starts to do so (because it developed an oncogene), it will thereby induce its own uncontrolled proliferation (autocrine loop), as well as the proliferation of neighboring cells.
    3. In addition, abnormal growth of endocrine glands often cause ectopic production of growth hormones that have secondary effects on other parts of the body.
      1. Protein kinases and related proteins Q
        There are six known classes of protein kinases and related proteins that can become an oncogene:
      2. Receptor tyrosine kinases Q that become constitutively (permanently) active like the epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR).
      3. Cytoplasmic tyrosine kinases like the Src-family, Syk-ZAP-70 family and BTK family of tyrosine kinases.
      4. Regulatory GTPases, for example, the Ras protein.
      5. Cytoplasmic Serine/Threonine kinases and their regulatory subunits, for example, the Raf kinase, and cyclin-dependent kinases (through overexpression).
      6. Adaptor proteins in signal transduction.
  2. Transcription factors.
    1. Important Oncogenes
      1. Numerous genes have been identified as proto-oncogenes.
      2. Many of these genes are responsible for providing the positive signals that lead to cell division.
      3. Some proto-oncogenes work to regulate cell death.
      4. As stated in the introduction to this section, the defective versions of these genes, known as oncogenes, can cause a cell to divide in an unregulated manner.
      5. This growth can occur in the absence of normal pro-growth signals such as those provided by growth factors.
      6.  A key feature of oncogene activity is that a single altered copy leads to unregulated growth.
      7. This is in contrast with tumor suppressor genes which must BOTH be defective to lead to abnormal cell division.
      8. The proto-oncogenes that have been identified so far have many different functions in the cell.
      9. Despite the differences in their 0normal roles, these genes all contribute to unregulated cell division if they are present in a mutant (oncogenic) form.
      10. The mutant proteins often retain some of their capabilities but are no longer sensitive to the controls that regulate the normal form of the protein.
      11. Selected oncogenes that have been associated with numerous cancer types are described in more detail on the pages that follow.
      12. To learn about a particular gene, choose from the list below.
        1. HER-2/neu (erbB-2): a growth factor receptor.
        2. RAS: a signal transduction molecule
        3. MYC: a transcription factor
        4. SRC: a protein tyrosine kinase.
        5. Htert: an enzyme that functions in DNA replication.
        6. Bcl-2: a membrane associated protein that functions to prevent apoptosis.

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