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Tumor promotion versus tumor initiation
Classic experiments in oncology established that EGF can promote growth of tumors that have already been initiated by chemical or viral carcinogens. This is an important finding. But promotion is not initiation. A promoter accelerates the growth of cells that
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- Classic experiments in oncology established that EGF can promote growth of tumors that have already been initiated by chemical or viral carcinogens. This is an important finding. But promotion is not initiation. A promoter accelerates the growth of cells that are already abnormal. An initiator creates the abnormality in the first place. EGF is a promoter, not an initiator.
- Moreover, the body has multiple endogenous mechanisms that protect against non-programmed mitogenic events. EGF bioavailability is tightly controlled by local peptidases. Receptor downregulation occurs rapidly after ligand binding, reducing sensitivity to prolonged stimulation. And PKC-mediated counter-regulation of tyrosine kinase activity provides an additional brake on excessive signaling. These built-in safety mechanisms mean that exogenous EGF application in healthy tissue does not result in uncontrolled proliferation.