INTRODUCTION

The cell is a complex array of networks – a protein communication system, with phosphorylation cascades transmitting messages from receptors at the surface to the nucleus. Individual proteins integrate signals from a diversity of activator molecules, transducing them through intracellular signalling pathways to various target or effector proteins. Circuits of this nature enable a cell to respond to external factors and to modify its own function. In particular, in this chapter we will look at the way in which growth factors and hormones regulate the processes of cell division and differentiation, and cell survival.

Proto-oncogenes have been identified as genes encoding protein members of cascades dedicated to the transmission of signals regulating growth and survival. The actions of proto-oncogene-encoded proteins are tightly controlled under normal circum stances. If such proteins are abnormal, or if there is too much of them, signals are deregulated, downstream transducing molecules are activated and there is excessive stimulation of cell growth and survival. When intracellular signal pathways are out of control, a cell may begin to multiply unceasingly in a way that can lead to cancer.

We define a proto-oncogene as the form the gene takes as it carries out its usual functions within a cell – it has the potential to become an oncogene. Proto-oncogenes may also be referred to as cellular oncogenes (conc). An oncogene is a mutated form of a proto-oncogene producing a protein, which stimulates uncontrolled growth and promotes cell survival. The homologous counterparts of certain oncogenes occur in retroviruses; these are viral oncogenes (v-onc). Oncogenes are dominant in the sense that only one allele needs to be mutated to cause cancer.

Many of the human oncogenes were discovered through the study of animal retro - viruses, acutely transforming RNA tumour viruses, whose genomes are reverse transcribed into DNA in infected cells. During the course of infection, retroviral DNA is inserted into the chromosomes of host cells. The retro viral oncogenes are derived from the normal cellular genes of the host which have been incorporated into the retroviral genome. In 1970, the first oncogene, now known as the SRC oncogene, was identified in a chicken tumour virus.