The Biology of Cancer - Vibrational Spectroscopy for Tissue Analysis - page 46

regulated by extracellular signals from the environment, as well as by internal
signals that monitor and coordinate the various processes that take place during
different cell cycle phases. An example of cell cycle regulation by extracellular
signals is provided by the effect of growth factors on animal cell proliferation.
Progression through the cell cycle is governed by a family of cyclin-
dependant kinases (CDKs) and their regulatory subunits, the cyclins [66]. As
cells enter the cell cycle from G 0 , D- and E-cyclins are synthesized sequen-
tially and both are rate limiting for S phase entry. In addition, as a result of
the activity of CDKs, exit from G 0 occurs with entry into the S phase.
A major cell cycle regularity point in many types of cells occurs late in
G 1 and controls progression from G 1 to S. This regulatory point was first
defined by studies of budding yeast ( Saccharomyces cerevisiae ), where it is
known as start . Once cells have passed start, they are committed to entering
the S phase and undergoing one cell division cycle.
The proliferation of most animal cells is similarly regulated in the G 1 phase
of the cell cycle. In particular, a decision point late in G 1 , called the restric-
tion point in animal cells, functions analogously to start in yeasts. In con-
trast to yeasts, however, the passage of animal cells through the cell cycle
is regulated primarily by the extracellular growth factors that signal cell
proliferation, rather than by the availability of nutrients. In the presence of
the appropriate growth factors, cells pass the restriction point and enter the
S phase. Once it has passed through the restriction point, the cell is commit-
ted to proceed through the S phase and the rest of the cell cycle, even in the
absence of further growth factor stimulation. On the other hand, if appropri-
ate growth factors are not available in G 1, progression through the cell cycle
stops at the restriction point. Such arrested cells then enter a quiescent stage
of the cell cycle called G 0 , in which they can remain for long periods of time
without proliferating. G 0 cells are metabolically active, although they cease
growth and have reduced rates of protein synthesis. As already noted, many
cells in animals remain in G 0 unless called on to proliferate by appropriate
growth factors or other extracellular signals. For example, skin fibroblasts
are arrested in G 0 until they are stimulated to divide as required to repair
damage resulting from a wound. The proliferation of these cells is triggered
by the platelet-derived growth factor, which is released from blood platelets
during clotting and signals the proliferation of fibroblasts in the vicinity
of the injured tissue [3,63,64]. Generally speaking, extracellular signals can
thus control cell proliferation by regulating progression from the G 2 to the
M phase as well as from the G 1 to the S phase of the cell cycle. It is believed
that the molecular events in regulating the key G1/S and G2/M phases of the
cell cycle are controlled by phosphorylation/dephosphorylation and particu-
larly by the degradation of cell-cycle regulators [67-69].
Although the proliferation of most cells is regulated primarily in G 1 ,
some cell cycles are instead controlled principally in G 2 . One example is
the cell cycle of the fission yeast Schizosaccharomyces pombe . The cell cycle of
this group is regulated primarily by control of the transition from G 2 to M,