CASE 2 CANCER: WHEN GOOD CELLS GO BAD
Many cancers arise when something goes wrong with the way a cell responds to a signal that leads to cell division or, in some cases, when a cell behaves as if it has received a signal for cell division when in fact it hasn’t. Defects in cell signaling that lead to cancer can take place at just about every step in the cell signaling process.
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In some cases, a tumor may form as the result of the overproduction of a signaling molecule or the production of an altered form of a signaling molecule. In other cases, the source of the problem is the receptor. For example, individuals with some forms of cancer have from 10 to 100 times the normal number of receptors for a signaling molecule called epidermal growth factor (EGF). As a result, the cell is more responsive to the normally low levels of EGF in the body. The EGF receptor is a receptor kinase, like the PDGF receptor. Under normal conditions, binding of EGF to its receptor leads to the controlled division of cells. However, in cancer, the presence of excess receptors heightens the response of the signaling pathway, leading to abnormally high gene expression and excess cell division. This is the case, for example, in certain breast cancers, in which an EGF receptor called HER2/neu is overexpressed.
Farther down the pathway, mutant forms of the Ras protein are often present in cancers. One especially harmful mutation prevents Ras from converting its bound GTP to GDP. The protein remains locked in the active GTP-