LEC 5: Disorders of Cell Growth

Question 1

Types of Abnormal Cell Growth

Answer 1

Neoplasia: new growths of cells in the body
Hyperplasia: abnormal increase in cell numbers
Hypertrophy: abnormal increase in cell size
Metaplasia: replacement of a mature cell type for another mature cell type
Dysplasia: replacement of a mature cell type for a less mature cell type

Question 2

Benign Tumours

Answer 2

-oma

Usually localised, non-invasive, resemble tissue of origin, often encapsulated

Question 3

Malignant Tumours

Answer 3

-sarcoma/-carcinoma

Invasive, rapid growth, spread to different sites

Question 4

Causes of Cancer: Heritability

Answer 4

Cancer predisposition syndromes, inheritance of a defective tumour suppressor or cancer susceptibility gene

Question 5

Causes of Cancer: Oncogenic Viruses

Answer 5

Viruses carrying genes that lead to cancer (e.g. HPV, EBV)

Question 6

Causes of Cancer: Environment

Answer 6

Increase mutation rate (e.g. diet, radiation, smoking, UV)

Question 7

Oncogenes

Answer 7

‘Jammed Accelerator’

• Genes/proteins that activate normal cell proliferation, but are mutated
• Results in uncontrolled proliferation
• Often ‘gain of function’ mutation (Dominant)

Question 8

Tumour Suppressor Genes

Answer 8

‘Defective Brakes;

• Genes/proteins that suppress normal cell proliferation, but are mutated
• Results in uncontrolled proliferation
• Often ‘loss of function’ mutation (Recessive)

Question 9

Tumour Suppressor Gene TP53

Answer 9

p53 can bind DNA (transcription factor)

• normally causes cell cycle arrest following DNA damage allowing for repair
• multiple cellular processes disrupted when p53 mutates

Question 10

Proto-oncogenes Control turn over of Cell Cycle

Answer 10

Proto-oncogenes encode proteins that normally control cell growth/proliferation
- When mutated they become oncogenes that cause self-sufficiency

Question 11

Common Gene Translocations in Cancer

Answer 11

• Burkitt’s Lymphoma: t(8;14)
• Acute Promyelocytic Leukaemia (APL): t(15;17)
• Acute Lymphoblastic Leukaemia (ALL): t(9;22)
• Ewing’s Sarcoma: t(11;22)

Question 12

Other Genetic Changes observed in Cancer

Answer 12

• Deletions (loss of tumour suppressor genes)
• microRNAs (increase expression of oncogenes, decrease expression of tumour suppressor genes)
• Epigenetic changes (post-translational modifications of histones, abnormal DNA methylation)

Question 13

6 Hallmarks of Cancer

Answer 13

1. Sustained proliferative signalling
2. Resistance to anti-growth signals
3. Immortality, no limit to cell divisions
4. Resistance to cell death through apoptosis
5. Sustained angiogenesis (formation of blood vessels)
6. Invasion and Metastasis

Question 14

Hallmarks of Cancer: Sustained Proliferative Signalling

Answer 14

Constitutively activated growth signalling, often driven by oncogenes (e.g. RAS, AKT)

Question 15

Hallmarks of Cancer: Resistance to Anti-growth Signals

Answer 15

Unregulated cell cycle progression, inactivated cell cycle checkpoints

Question 16

Hallmarks of Cancer: Immortality (No limit to cell divisions)

Answer 16

• Telomere length extension by Telomerase (Hayflick Limit: critically shortened telomeres sensed as DNA damage = result in apoptosis)
• Inactivated cell death pathways

Question 17

Hallmarks of Cancer: Resistance to Programmed Cell Death

Answer 17

e. g. Activation of survival signalling pathways such as AKT

- BCL2 overexpression in cancer prevents the induction of apoptosis

Question 18

Hallmarks of Cancer: Sustained Angiogenesis

Answer 18

Activated vascular endothelial growth factor (VEGF) signalling allows for formation of new blood vessels

Question 19

Hallmarks of Cancer: Invasion and Metastasis

Answer 19

Loss of cell-cell interactions, contact inhibition, anchorage dependence
- clumps or foci develop and cells able to spread

Question 20

Tumour and Stroma

Answer 20

Tumour: transformed or neoplastic cells, proliferating

Stroma: normal cells (normal DNA), CT, blood vessels, host immune/inflammatory cells. Provides support to enable tumour growth