the biology of cancer

Question 1

cancer

Answer 1

a term used for diseases in which abnormal cells divide without control and are able to invade other tissues.

Question 2

hyperplasia

Answer 2

over proliferation of cells that appear otherwise normal

Question 3

metaplasia

Answer 3

normal in appearance but in wrong place (usually from adjacent tissue layer)

Question 4

dysplasia

Answer 4

cells that appear abnormal; often increased nuclear to cytoplasmic ratio and loss of features of differentiation

Question 5

adenomas/polyps/warts

Answer 5

larger growths of dysplastic cells

Question 6

cancer/malignant tumour

Answer 6

invading other tissue, usually by breaking through BM of epithelium.

Question 7

what is a cancer cell?

Answer 7

• divides continuously and inappropriately
• no longer maintains its original function
• some cancer cells must have the ability to spread to other sites

Question 8

hanahan and weinberg

Answer 8

1) insensitivity to anti-growth signals
2) self-sufficiency in growth signals
3) evading apoptosis
4) sustained angiogenesis
5) limitless replicative potential
6) tissue invasion and metastasis

Question 9

cancer is clonal- what does this mean

Answer 9

all cells share some mutations with common ancestors but they also develop subclones (subpopulations)

Question 10

carcinogens resulting in mutations

Answer 10

• carcinogens lead to a high rate of mutation.
• most mutations not in genes or don’t affect gene function
• most that affect gene do not affect features of cell that would lead to cancer
• need to identify those mutations that do affect function of genes that regulate proliferation, apoptosis, immortality etc- these are ‘driver’ mutations
• all other mutations that are not relevant to the promotion of cancer are ‘passenger’ mutations.

Question 11

(proto)-oncogenes

Answer 11

• promote cell proliferation (most regulate proliferation

- gain of function mutations in cancer

Question 12

tumour suppressor (TS) genes

Answer 12

• inhibit events leading to cancer (most regulate proliferation, immortality and apoptosis)
• loss of function mutations in cancer

Question 13

proliferation: the cell cycle

Answer 13

Cell division (proliferation) progresses through the following two main phases
M phase
S phase
interspersed by two “gap” phases (G1 & G2)
• Cells can also enter G0 (long-term inactivation of cell cycle)
• Mitogens (e.g. EGF) promote proliferation of cells in G0 & G1

Question 14

EGF: epidermal growth factor

Answer 14

single gene regulates restriction point (termed ‘start’ in yeast)

Question 15

Proliferation: cell cycle control

Answer 15

• the restriction (R) point in G1 phase (beyond which a cell is committed to cell division without growth factors)
• DNA damage checkpoints in late G1 and G2
• metaphase checkpoint (spindle attachment checkpoint) in M.

oncogenes promote proliferation (via restriction point).
tumour suppressors inhibit proliferation

Question 16

restriction point control

Answer 16

in the G1 phase, after which the cell is ‘committed’ to the cell cycle, after which the extracellular signals are no longer required to stimulate proliferation.
The defining biochemical feature of the restriction point is the activation of G1/S- and S-phase cyclin-CDK complexes, which in turn phosphorylate proteins that initiate DNA replication, centrosome duplication, and other early cell cycle events.

Question 17

processes in limiting the number of times a cell can divide

Answer 17

• senescence- cells into G0; don’t proliferate
• apoptosis- programmed cell death; response to DNA damage, cell stress etc.

Both processes severely restrict tumour growth. Both processes much be overcome to develop cancer.

Question 18

senescence

Answer 18

• cells in senescence are metabolically active, but have irreversible lost ability to re-enter cell cycle
• normal cells have a finite proliferative capacity (Hayflick limit)
• at this point they stop dividing and go into replicative senescence

Question 19

telomere shortening

Answer 19

normally shortening results in senescence.

cells only bypass senescence and reach ‘crisis’ if key tumour suppressors (such as P53) are inactivated.

Question 20

telomere loss leading to chromosome instability

Answer 20

Telomere loss can lead to incorrect DNA repair and chromosome fusion. especially fusion between ends of sister chromatids which are then torn apart at anaphase. this results in translocations.

Question 21

excess telomere shortening leading to crisis

Answer 21

• damage to chromosomes will eventually make the cell unlivable
• cells undergo apoptosis if they can.
• ‘genetic catastrophe’ is so severe it triggers apoptosis even in the absence of p53

Question 22

TERT

Answer 22

telomerase reverse transcriptase.
TERT regenerates telomeres, to avoid genetic catastrophe. Almost every cancer has telemorase reactivated; usually after significant chromosome rearrangement has occurred

Question 23

apoptosis

Answer 23

triggered by damage to cell/DNA, stress, oncogene activation. uses energy to kill cell without releasing contents and so avoid inflammation- uses caspases. caspases digest proteins. P53 is a regulator of apoptosis, as are many tumour suppressors

Question 24

key genes in control

Answer 24

2 key genes in control, proliferation, senescence and apoptosis:
p53 and Rb (key regulator of restriction point)

Question 25

sustained angiogenesis

Answer 25

• O2 and other nutrients supplied by vasculature are essential for cell function and survival.
• newly arisen tumours must promote angiogenesis to survive
• hypoxia induced factor 1alpha (1α)

Question 26

VEGF

Answer 26

vascular endothelial growth factor.
• induces angiogenesis (new vessel growth)
• Promotes endothelial precursor cell formation in bone marrow (travel to tumour)

Question 27

imperfect vasculature

Answer 27

vascularisation is disorganised.

• probably due to imbalance of signals for growth vs. differentiation
• leaky due to imperfect cell-cell junctions

Question 28

tissue invasion and metastasis

Answer 28

• Loss of adhesion – delamination* (e.g. E-cadherin loss)
• Activation of endogenous metalloproteinases
• Invasion of leaky blood vessels (or lymph system)
• Blood flow: millions travel, few survive (immune surveillance)

Question 29

secondary tumours

Answer 29

2 theories:

• ‘seed and soil’ therory; cells move to a part of a body where the environment is suitable e.g. stomach -> liver, breast -> lung, lung -> anywhere
• capillary beds: tumour cells are larger and tend to get stuck in the capillary bed of the next target organ on in the circulatory system