Review article: The role of oncogenes, tumour suppressor genes and growth factors in oral squamous cell carcinoma: a case of apoptosis versus proliferation.
Mutation, deactivation and disregulated expression of oncogenes and tumour-suppressor genes may be involved in the pathogenesis of oral squamous cell carcinoma (SCC). Deactivation of the p53 tumour-suppressor gene allows cell proliferation and blocks apoptosis of malignant oral keratinocytes. Mutation in the ras oncogene results in persistent mitogenic signalling. Upregulatioed c-Myc expression, in the presence of growth factors, provides an additional proliferative signal. Loss of retinoblastoma tumour-suppressor gene (Rb) function may contribute to oral keratinocyte hyperproliferation and recent evidence suggests that simultaneous deactivation of both p53 and Rb is required for tumourigenesis. Enhanced Bcl-2 and reduced Fas expression inhibit tumour cell apoptosis and may convey resistance to cytotoxic drugs and T cell-mediated cytotoxicity, respectively. Exogenous mutagens such as tobacco, alcohol and viral oncogenes may cause altered expression of oncogenes and tumour-suppressor genes in some cases of oral SCC. The impact of these mechanisms on future therapies for oral SCC is highlighted.
Sugerman
P B
PB
Oral Biology and Pathology, The University of Queensland, St Lucia, Australia.
Joseph
B K
BK
Savage
N W
NW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000628:therapy / Q000821:virology; D002455:Cell Division / Q000235:genetics; D053222:Fas Ligand Protein; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D009062:Mouth Neoplasms / Q000235:genetics* / Q000628:therapy / Q000821:virology; D009857:Oncogenes / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes / Q000502:physiology
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D006133:Growth Substances; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2