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Great progress has been made over the last fifteen years on our knowledge of tumours and healthy tissues, in particular on regulating mechanisms for cell division and relationships within a multicellular organism.

Many transmission signals between cells have been elucidated, transmitting the order to multiply or to suicide or to differentiate when no cell division is necessary.

During cancer, these very subtle regulating mechanisms may be deregulated with some signal receptors being over-expressed, over-activated, other molecules being abnormal and permanently transmitting multiplication or death orders.

On the following diagram, the permanent need for constant small stimulation of breast cells by growth factors is represented.

A normal mammary cell [1] has, on its internal surface (close to the basal membrane), Epidermal Growth Factor receptors [2] which are represented as little yellow or red men. When the number of receptors is normal [3], the cell maintains a constant moderate activity in relation to the signals which are transmitted from the receptors to the nucleus. On cell [4], an over-expression of ErbB-2 receptors (in red) is observed, thus the smallest stimulation by a growth factor will induce uncontrolled cell multiplication. This is one of the mechanisms of cell disordered multiplication during cancer.

Most membrane receptors are transmembrane molecules. In the presence of their specific growth factor, the receptors will dimerise and this dimerisation induces a phosphorylation of intracell tyrosine kinases, thus initiating the signal transmission towards the nucleus. This is shown on the following diagram.

On this diagram, the growth factor (blue ball) can dimerise two adjacent receptors which may be slightly different, but are complementary (as generally observed in clinical situations). Dimerisation induces the activation of tyrosine-kinase (red balls with red rays). This activation is transmitted to proteins immediately adjacent to the cell membrane (such as the Ras protein).