The cell cycle is a complex mechanism that results in cell growth and propagation. In eukaryotes, such as humans, the cycle is divided into G1, S, G2, and M phases, where M represents the process of mitosis (i.e. cell division), S represents “synthesis” (as in DNA synthesis), and G represents “gap”. Different cell types proceed through the cycle at different rates at different times.
Cell cycle regulation usually brings to mind cyclins and CDKs (cyclin dependent kinases), but the entrance of a cell into the cycle (as opposed to quiescence, G0) depends on growth factors. As outlined by Jones and Kazlauskas in a review in FEBS Letters in 2001, growth factors play a role in progression through the G1 to S interval, determining whether a cell will divide. Growth factors are proteins or peptide hormones that act on receptors on the cell surface, and different factors affect different cell types and tissues. Disrupted regulation of these factors can result in cancer due to their effects on cell division and growth, and as such are associated with oncogenes and tumor suppressors.
The effect of growth factors on the cell cycle was first recognized in the 1980s, as noted by Zetterberg in the journal Cytometry in 1984. Since that time, a number of protein factors (which occur in various subtypes often noted by Arabic numbers or Greek letters) have been recognized, including the following as outlined by Dr. Michael King at Indiana University and various studies:
Controllers of cell growth, white blood cells, and connective tissue – platelet derived growth factor (PDGF), fibroblast growth factor (FGF, also known as basic FGF, or bFGF), epidermal growth factor (EGF), transforming growth factor (TGF), connective tissue growth factor (CTGF)
Smooth muscle, blood vessels, and endothelium – vascular endothelial growth factor (VEGF)
Neuron-specific – neurotrophins such as nerve growth factor (NGF) and brain-derived nerve growth factor (BDNF)
Promotes red blood cell production in the bone marrow – erythropoietin (EPO), which is produced specifically by the kidney
Promote proliferation and fetal development – insulin-like growth factor (IGF)
Stem cell proliferation in adult bone marrow – colony stimulating factor (CSF), which is lineage-specific (granulocyte (G-CSF) and macrophage (M-CSF)).
Cytokines are growth factors secreted by leukocytes (white blood cells). They include the interleukins and interferons, which promote inflammatory cell proliferation (such as T cells). Adipose tissue is also a source of growth factors, called adipokines, that promote inflammatory and fat cell proliferation: tumor necrosis factor (TNF; TNF alpha is also known as cachectin and TNF beta is also known as lymphotoxin), adiponectin, monocyte chemoattractant protein (MCP), and plasminogen activator inhibitor (PAI).
