What causes cells to proliferate?

Cells initiate proliferation after receiving external signals called mitogens, from adjacent cells. Mitogens work by overriding the internal “brakes” within the cell, and allowing it to move forward in the cell cycle. An example of a prominent mitogen is platelet-derived growth factor (PDGF). When the blood clots, platelets in the clot release their contents. Serum is found to be highly effective in promoting cell proliferation, indicating the presence of one or more mitogens. This was confirmed when extracts from platelets were shown to induce fibroblast proliferation. The substance found in the extracts was PDGF. PDGF induces cell proliferation by attaching to PDGF receptor alpha or PDGF beta. This results in receptor dimerization and autophosphorylation. 

DNA damage also contributes to cell proliferation. DNA damage may induce cell cycle arrest, to allow for the cell to repair any errors. However, if the damage is not repaired correctly and the cell continues to divide, the accumulation of DNA alterations may lead to mutations. These mutations then place cells at a higher risk of becoming malignant. For example, mutations in the tumor suppressor gene p53 are the most accumulated mutations in cancer. In a mutated p53 gene, the protein is unable to regulate cell proliferation correctly and unable to initiate apoptosis in cells with damaged DNA. Thus, DNA damage accumulates within the cells as a result.