Cell proliferation in cancer
The first fundamental characteristic of cancer is its proliferative potential. Unlike normal cells, which carefully control and restrict proliferation in order to maintain tissue homeostasis, cancer cells develop strategies that enable them to gain control of their proliferative capacity. The loss of key proliferation-associated restrictions both enables the continuous and exponential growth of cell numbers, leading to tumour development, and permits the local invasion of tissue by cancer cells, a process that in normal cell and tissue physiology is prevented by a complex system of locally produced signalling factors and cell to cell interactions (King and Robins, 2006). The loss of processes such as density-dependent inhibition, contact inhibition and anchorage dependence means that cancer cells do not stop proliferation once the tissue reaches a specific density or when cells come into contact with one another. In addition, cancer cells appear to be able to grow and divide without attachment to the supporting structures in the microenvironment.
Important signalling pathways are commonly altered in cancer as a result of oncogene expression. Oncogenes can abnormally code for growth factors such as platelet-derived growth factor (PDGF) and transforming growth factor-а (TGFa). The presence of their cognate receptors on the cancer cell then leads to an autonomous growth loop. Amplification of oncogenes can also lead to over-expression of cell surface growth factor receptors, leading to cell growth in the context of lower concentrations of growth factor. Alternatively, growth factor receptors on the cancer cell surface, such as receptor kinases, can be constitutively activated and therefore do not require the presence of growth factors for signalling. Because they are abnormally activated, these receptors permit the relevant intracellular signalling molecules to be activated, resulting in proliferation signals being sent further down the signalling pathway, ultimately reaching the nucleus.
Cytoplasmic proteins that make up the signalling pathways from the cell surface to the nucleus can themselves be permanently altered into their activated form, leading once again to continuous proliferation signals in the malignant cell. Examples of these pathway signal transducers include the ras, abl and raf proteins. Within the nucleus, transcription factors are fundamental to gene expression as they recognise and bind to specific parts of the gene and recruit RNA polymerase for gene transcription. Deregulation of this part of the pathway will lead to over-expression of oncogenes or reduced expression of tumour suppressor genes.