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 and malignant tumours

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 together)

• Can normally be removed by surgery and they rarely return

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 (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 cells cycle (e.g. if DNA damage detected)

• OR cause self-destruction (apoptosis) of potential tumour cells (e.g. 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 (e.g. 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 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

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