Fig. 1.6 Important membrane proteins.
(A) Different calcium ion channels controlling the intracellular calcium concentration. (B) G-protein receptors;
the example shows adrenergic activation of the adenylate cyclase (Ac). (C) Tyrosine kinase receptors; the example shows EGF-mediated phosphorylation of
intracellular downstream targets.
of ear). However, many epithelial tissues, as well as hemato-
lymphopoietic cells, depend on a continuous replenishment
of their cell pools. Other tissues have retained a regenerative
capacity, e.g. liver stem cells, that make it possible to regener-
ate the organ after tissue damage. The detailed mechanisms of
cell division can be recapitulated in a cell biology textbook. In
brief, the cell cycle consists of four phases, the G1, S, G2, and
M phases. Resting cells are in a constant GO phase that has a
direct transition from the G1 phase. G phases are gap phases,
S indicates the synthesis phase in that the genomic material
is doubled, and M indicates the phase of mitosis, in that two
daughter cells are created (Fig. 1.7A). In order to assure a proper
cell division with equal distribution of the genomic material in
the daughter cells, several checkpoints (after G1, S, and G2)
must be passed to allow for a continuation of the cell cycle. If
the requirements at a checkpoint are not met, the cell is not
allowed to continue; it might even go into apoptosis.
In light microscopy, mitotic figures represent the M phase, i.e.
the distribution of chromosomes into the opposite poles of a cell
(Figs. 1.7B, C). Mitotic figures are rare in normal tissue; in nor-
mal liver, about 1-2 mitoses can be observed per 10,000 cells.
In rapidly dividing cancer tissue, the frequency of mitotic figures
can be much higher, depending on the underlying cell type.
The regulation of the cell cycle is very complex. In general,
uncontrolled activation of the cell cycle is a basic feature of all
tumors. The reasons for uncontrolled cell cycle activation can be
either the loss of inhibitory gene functions (inactivated tumor
suppressor genes) or the activation of cell cycle promoting gene
functions (activated oncogenes). The detailed mechanisms of
carcinogenesis are described in Part II of this chapter.