Cancer and the Cell Cycle

• Cells escaped growth control mechanisms
• Stages
• Accumulation of somatic mutations
• Genes for proteins for detection or repair of damaged DNA
• Increases mutation rate
• Development of genetic instability
• Changes in genes in cancer cells
• Duplications, deletions of parts of chromosomes, DNA translocation

ONCOGENES

• Initially identified as viral gene
• Proto-oncogenes
• Genes within normal DNA of every cell
• Mutatated, activated ￫ Product ￫ Tumour
• Influence is direct or indirect 
• e.g. mitogen-activated protein kinase (MAPK) pathway
• Amino acid substitutions @ 21 or 61 in Ras
• Activating ERK MAPK pathway

TUMOUR SUPPRESSOR GENES

• Mutations ￫ Loss of function that restrains cell growth
• RB gene
• Normal: non-phosphorylated RB prevents cell proliferation
• Phosphorylation by CDK ￫ S phase
• Retinoblastoma
• p53
• Tumour suppressor 
• Loss or mutated in >50% all human cancers
• Damage to DNA ￫ Nuclear phosphoprotein ￫ Blocking progression through cell cycle or apoptosis
• Direct mutation. Mutations of other genes affecting p53 expression or function.