Molecular regulation

Cellular proliferation and differentiation is a balance of elements which tend to enhance or retard each function. Growth factors have their signal transduced at the nucleus into a complex web of activation of two types of gene:

• proto-oncogenes:
  • normal cellular genes which may be switched on in an abnormal manner or may produce too much of their gene product, so stimulating excessive cellular proliferation - they become oncogenes
  • act via tyrosine kinase production, and hence protein phosphorylation, G protein or nuclear protein production
  • can be activated by point mutations, translocations of regions of chromosomes, or duplication and hence excessive production of the proto-oncogene
  • an example of an oncogene is ras which is derived from a proto-oncogene by a point mutation and is implicated in a variety of human cancers
• tumour suppressor genes:
  • normal cellular genes hypothesised to switch off or suppress cellular proliferation
  • the inactivation or under-expression of such genes could stimulate over-proliferation of cells
  • may be disrupted by the same molecular mechanisms as those affecting proto-oncogenes, e.g. point mutation
  • an example of a tumour suppressor gene is p53 which is variably mutated in its associations with human liver, lung, stomach, colon and breast cancer