UNIT 3 DAY 7 - DEATH OR CANCER

Question 1

Why, when a liver cell stops dividing and differentiates into a cell specialised to perform live functions, is it doing something that none of its ancestors have done during the past billion years?

Answer 1

• We arose entirely from a line of endlessly proliferating (growing) germ-line cells (sperm+egg)
• Some cells will differentiate into germ cells and somatic cells
• After dozens of the cell divisions needed to create and adult soma from a single cell, we find a cell, say a liver cell, that must play a specialised role in the life of multicellular individuals

Question 2

What is the biggest question about cancer? Why doesn’t it happen even sooner and more frequently than it actually does?

Answer 2

• How is it possible that any of us can live several decades without dying of cancer?
• Cancerous cells are merely cells doing their normal thing: growing and dividing
• They do that for long period of time or else everyone would die from cancer at a young age

Question 3

What are the mechanisms that must be in place to prevent mutant cells from reproducing uncontrollably?

Answer 3

• P53
• safe catch principle

Question 4

What is the safe catch principle?

Answer 4

• Control of cell division
• The body has multiple safety-catch were if the mechanism of cell division are failing then safety catches will stop cell growth or cause cell to self-destruct

Question 5

cancer

Answer 5

defective form of normal gene that acts in detection and rectification of abnormal DNA structure

Question 6

P53 gene

Answer 6

• makes a protein that protects against cancer by regulation expression of genes

Question 7

study that studies cancer

Answer 7

Campisi (2003)

Question 8

What is cancer?

Answer 8

• cellular phenomena that occurs because cells acquire certain abnormal properties
• these allow cells to from multicellular masses
• have potential to kill organisms

Question 9

malignant phenotypes of cancer

Answer 9

• loss of growth control
• resistance to apoptosis or programmed cell death
• extended replicative lifespan
• ability to invade surrounding tissue
• ability to colonise and survive in ectopic environment

Question 10

What causes cancer?

Answer 10

• acquisition of mutations

Question 11

What kind or organisms get cancer?

Answer 11

• affects complex organisms with renewable tissues

Question 12

what makes complex organisms susceptible to cancer?

Answer 12

• Complex organisms have renewable tissues
• Renewable tissues allow adult organisms to replace cells that are lost through randomness, pathological or catastrophic damage
• Cell (proliferation) growth that occurs in renewing tissues puts the genome at great risk for acquiring and creating mutations

Question 13

strategies for suppressing cancer

Answer 13

• caretaker genes
• gatekeeper genes

Question 14

caretaker proteins

Answer 14

• protect genomes from developing possible concerned cancer causing mutations
• operate within cell
• evolved early in time
• present in single celled organisms

Question 15

gatekeeper proteins

Answer 15

• eliminate the growth of potential cancer causing cells
• operating within tissues
• organisms activate when damage is beyond repair
• never evolved
• came with multicellular organisms

Question 16

cellular senescene

Answer 16

cells no longer can divide

Question 17

angiogenesis

Answer 17

ability to attract blood supply

Question 18

Nucleotide Excision pathway (example of caretaker)

Answer 18

• A DNA-repair pathway that removes and replaces damaged nucleotides, particularly those that distort the DNA helix

Question 19

Oncogene

Answer 19

a type of gene which if mutated from its normal condition can cause cancer

Question 20

P53 gene (example of gatekeeper)

Answer 20

• control apoptosis and cellular senescene responses
• operates in complex organisms

Question 21

apoptosis

Answer 21

programmed cell death

Question 22

longevity

Answer 22

average.maximum lifespan of organism cohort

Question 23

aging

Answer 23

• decline in organismal fitness
• coincides with increased age

Question 24

Why would tumour-suppressing genes promote longevity?

Answer 24

• curtailing development of malignant tumours
• loss of tumour suppressor function should shorten average lifespan by increased incidence of cancer

Question 25

What tumour-suppressing gene causes retard aging and, conversely, what type of tumor suppressor genes promote aging?

Answer 25

• Caretaker and Gatekeeper
  -DNA-repair pathways increases both the incidence of cancer and the rate at which specific aging phenotypes develop
  -Gatekeeper mechanisms of apoptosis and cellular senescence suppress the development of cancer and promote the development of specific aging phenotypes

Question 26

apoptosis role

Answer 26

• ensures cells die without releasing destructive degradative enzymes or triggering inflammatory reactions

Question 27

apoptosis role during embryonic development

Answer 27

• eliminate excess cells or cells that haven’t made intellectual connections

Question 28

apoptosis role during tissue maintenance

Answer 28

• in complex organisms, apoptosis is essential for homeostasis maintenance of renewable tissues –> apoptosis eliminates dysfunctional or damaged oncogenic cells

Question 29

apoptosis role in cancer cells

Answer 29

• cancer cells acquire mutations that allow them to evade normal signals and mechanisms that cause apoptic death

Question 30

Why is aging an evolutionary puzzle?

Answer 30

• organisms are not programmed for age, NS selects for fitness, survival, etc –> not genes that harm these things (aka aging)

Question 31

evolution of aging phenotypes (according to williams)

Answer 31

• pleiotropic theory of senescene –> strong selection for traits beneficial in youth, regardless of deterious effect in old age, when fewer individuals are able to be selected

Question 32

evolution of aging phenotypes (according to williams theory)

Answer 32

• natural selection favours the youth reproductive years, not at older age, not at older age traits beneficial early on may be harmful later on
• outcomes of decline in selection; germlines only harmful later in life, not eliminated, traits beneficial early on are retained
• apoptosis might contribute to aging

Question 33

for mice with the heightened P53 activity, the advantage that resulted from having the extra P53, but the accompanying disadvantage in terms of aging

Answer 33

• leads to decreased cancer, decreased lifespan and leads to premature aging

Question 34

will we be able to manipulate tumour-suppressing mechanisms without accelerated aging?

Answer 34

• likely difficult due to antagonistic pleiotrophy
• potential in P53 regulation to decreased tumours without increased aging … but more work needed

Question 35

how does the figure on liver cells illustrate “why the biggest question about cancer, is therefore, why it doesn’t happen even sooner and more frequently than it actually does?”

Answer 35

• liver cells in a parent do not give rise to the liver cells in its offspring
• all cells in the adult body arise from germ lines cells, which themselves arose from earlier germ line cells, stretching back into the distant past
• when a liver cell stops dividing and becomes a dedicated liver cell, never to divide again, it is doing something that it has never done before in the past billion years
• insuring that all cells stop dividing, when they are descended from cells that have repeatedly divided for a billion years, is not easy to accomplish