8.2.3 Gene expression and cancer

• Describe how tumours and cancers form

  ● Mutations in DNA / genes controlling mitosis can lead to uncontrolled cell division

  ● Tumour formed if this results in mass of abnormal cells

  ○ Malignant tumour = cancerous, can spread by metastasis

  ○ Benign tumour = non-cancerous

  
• Compare the main characteristics of benign tumours

  • Usually grow slowly (cells divide less often)
  • Cells are well differentiated / specialised
  • Cells have normal, regular nuclei
  • Well defined borders and often surrounded by a capsule so do not invade surrounding tissue
  • Do not spread by metastasis (as cell adhesion molecules stick cells together)
  • Can normally be removed by surgery and they rarely return
• Compare the main characteristics of malignant tumours

  • Usually grow faster (cells divide more often)
  • Cells become poorly differentiated / unspecialised
  • Cells have irregular, larger / darker nuclei
  • Poorly defined borders and not encapsulated so can invade surrounding tissues (growing projections)
  • Spread by metastasis - cells break off and spread to other parts of the body, forming secondary tumours (due to lack of adhesion molecules)
  • Can normally be removed by surgery combined with radiotherapy / chemotherapy but they often return
• Describe the function of tumour suppressor genes

  Code for proteins that:

  ● Inhibit / slow cell cycle (eg. if DNA damage detected)

  ● OR cause self-destruction (apoptosis) of potential

  tumour cells (eg. if damaged DNA can’t be repaired)

  
• Explain the role of tumour suppressor genes in the development of tumours

  ● Mutation in DNA base sequence → production of non-functional protein

  ○ By leading to change in amino acid sequence which changes protein tertiary structure

  ● Decreased histone acetylation OR increased DNA methylation → prevents production of protein

  ○ By preventing binding of RNA polymerase to promoter region, inhibiting transcription

  ● Both lead to uncontrolled cell division (cell division cannot be slowed)

  
• Describe the function of proto-oncogenes

  • Code for proteins that stimulate cell division (eg. through involvement in signalling pathways that control cell responses to growth factors)

  
• Explain the role of oncogenes in the development of tumours

  An oncogene is a mutated / abnormally expressed form of the corresponding proto-oncogene

  ● Mutation in DNA base sequence → overproduction of protein OR permanently activated protein

  ○ By leading to change in amino acid sequence which changes protein tertiary structure

  ● Decreased DNA methylation OR increased histone acetylation → increases production of protein

  ○ By stimulating binding of RNA polymerase to promoter region, stimulating transcription

  ● Both lead to uncontrolled cell division (cell division is permanently stimulated)

  
• Suggest why tumours require mutations in both alleles of a tumour suppressor gene but only one allele of an oncogene

  ● One functional allele of a tumour suppressor gene can produce enough protein to slow the cell cycle OR cause self-destruction of potential tumour cells → cell division is controlled

  ● One mutated oncogene allele can produce enough protein to lead to rapid / uncontrolled cell division
• Explain the relevance of epigenetics in cancer treatment

  Drugs could reverse epigenetic changes that caused cancer, preventing uncontrolled cell division. For example:

  ● Increasing DNA methylation OR decreasing histone acetylation of oncogene

  ○ To inhibit transcription / expression

  ● Decreasing DNA methylation OR increasing histone acetylation of tumour suppressor gene

  ○ To stimulate transcription / expression
• Explain the role of increased oestrogen concentrations in the development of some (oestrogen receptor-positive) breast cancers

  1. Some breast cancers cells have oestrogen receptors, which are inactive transcription factors
  2. If oestrogen concentration is increased, more oestrogen binds to oestrogen receptors, forming more oestrogen-receptor complexes which are active transcription factors
  3. These bind to promoter regions of genes that code for proteins stimulating cell division
  4. This increases transcription / expression of these genes, increasing the rate of cell division
• Suggest how drugs that have a similar structure to oestrogen help treat oestrogen receptor-positive breast cancers

  ● Drugs bind to oestrogen receptors (inactive transcription factors), preventing binding of oestrogen

  ● So no / fewer transcription factors bind to promoter regions of genes that stimulate the cell cycle