Cell proliferation

The cell cycle (Fig. 3.36) is the sequence of events
whereby a proliferative cell divides into two. The
newly-born cell increases its volume and mass during
a post-mitotic interphase (G1 phase), doubles its
complement of chromosomes during a DNA synthesis
phase (S phase), increases further in volume and
mass during a post-synthetic interphase (G2 phase)
and then divides by mitosis and cytokinesis (M
phase). During the G1 phase (and for some cell types
also during the G2 phase), the cell may exit the cycle
and enter a quiescent state, the G0 phase. Whether it
does or not is determined by intrinsic signals or signals
from neighbouring cells.
The time required to complete a eukaryotic cell
cycle depends on the cell type. Embryonic cells do not
need to grow between divisions and can complete a
cell cycle in 8 min. The most rapidly dividing somatic
cells have cycling times of 10–24 hours; liver cells
divide about once a year and mature neurons never
divide.
3.9.2 Control of cell proliferation
Genetic infl uences
Regulation of the cell cycle is a balance between gene
products that promote cell replication and those that
deter cell replication. Genes that can cause resting
cells to divide are classifi ed as proto-oncogenes, while
genes that can prevent a cell from dividing are called
tumour suppressor genes. The protein products of
tumour suppressor genes serve as transducers of antiproliferative
signals.
Cell signalling
Two major cell surface receptor mechanisms mediate
the effects of extracellular messengers on intracellular
processes. Many hormones, including glucagon,
ACTH and adrenaline, interact with plasma membrane-
bound receptors to activate adenylyl cyclase
to increase the production of cyclic AMP. Numerous
other agents, including peptide hormones and growth
factors, interact with receptors to induce a rapid turnover
of phosphatidylinositol in the plasma membrane
of target cells to produce diacylglycerol. Diacylglycerol
can markedly stimulate calcium-dependent protein
kinase C, which catalyses the phosphorylation of preexisting
proteins. Phosphorylation is an important
mechanism for controlling the activities of enzymes
involved in cell proliferation and many other cellular
systems. Cyclic AMP inhibits receptor-mediated
phosphatidylinositol turnover, thereby decreasing
diacylglycerol production and preventing the activation
of protein kinase C (Anderson et al., 1985).