of the MAPK pathway, ultimately expressing proteins that stimulate cell cycle progression. It is likely that most, if not all, cancers have some mutation in the Ras-Raf-MAPK pathway, most commonly in Ras. These mutations allow the pathway to be constitutively activated, regardless of the presence of mitogens. Resistance to anti-mitogens Cell proliferation is often regulated by not only external mitogens but also by anti-mitogens, which inhibit cell cycle progression past G1. In normal cells, anti-mitogenic signaling as a result of DNA damage, preventing the cells from replicating and dividing. Tumor cells that are resistant to anti-mitogens allow the cell cycle to move forward when it should be prevented by some anti-mitogenic mechanism. This resistance to anti-mitogens might simply arise from overstimulation by positive mitogens. In other cases, tumor cells possess loss-of-function mutations in some part of the anti-mitogenic pathway. For example, consider the well-known anti-mitogen, transforming growth factor (TGF-𝝱). TGF-𝝱 works by binding to cell-surface receptors and activating the Smad gene regulatory proteins. Smad proteins then trigger an increase in p15, which inhibits cyclin D1 and prevents cell cycle progression. In many cancers, there is a loss-of-function mutation in the Smad proteins, thus negating the entire anti-mitogenic pathway. Multiple mutations required Not just one but multiple mitogenic mutations are required for cancer to proliferate. Generally, multiple mutations in different subsystems (an oncogene and a tumor suppressor gene) are the most effective at causing cancer. For example, a mutation that hyperactivates the oncogene Ras and another that inactivates the tumor suppressor pRb is far more tumorigenic than either protein alone. Tumor cells are also resistant to the hyperproliferation stress response. Normal cells have apoptotic proteins that will respond to an overstimulation of mitogenic signaling pathways by triggering cell death or senescence. This generally prevents the onset of cancer from a single oncogenic mutation. In tumor cells, there is generally another mutation that inhibits apoptotic proteins as well, suppressing the hyperproliferation stress response. Use in immunology Lymphocytes can enter mitosis when they are activated by mitogens or antigens. B cells specifically can divide when they encounter an antigen matching their immunoglobulin. T cells undergo mitosis when stimulated by mitogens to produce small lymphocytes that are then responsible for the production of lymphokines, which are substances that modify the host organism to improve its immunity. B cells, on the other hand, divide to produce plasma cells when stimulated by mitogens, which then produce