JM Lecture 53: Cell cycle checkpoints and cancer

Question 1

What are primary cells?

Answer 1

cells with a finite lifespan that are directly removed from the organism

Question 2

What are immortalized cells?

Answer 2

cells which have an unlimited lifespan

Question 3

What are transformed cells?

Answer 3

immortalized cells that have acquired certain properties including anchorage-independency or failure to stop growing upon contact with other cells

Question 4

What are tumorigenic cells?

Answer 4

transformed cells that have the additional property of being able to form a tumor in the animal

Question 5

What is the Warburg effect?

Answer 5

enhanced glycolytic rate in tumor cells

relies on glycolysis for ATP rather than TCA cycle (not necessarily due to a low O2 environment)

Question 6

Which cancer cells normally become anchorage independent and how do they do so?

Answer 6

epithelial carcinomas

loss of restriction point requiring adhesions (overcome 1st check-point)

Question 7

Define contact inhibition.

Answer 7

the property found in normal cells where they do not grow upon contact with neighboring cells, resulting in a flat layer of cells

Question 8

What can results in the lack of growth factor dependence in cancer cells?

Answer 8

Rb is lost
cyclin B expression increases
loss of p15 and p16
missense mutation in Cdk6 or Cdk4 enzyme preventing binding

Question 9

What is the ploidy of cancer cells and how is it achieved?

Answer 9

anything other than diploid

results from deletions, gene amplification, chromosomal translocation

Question 10

What is angiogenesis?

Answer 10

recruitment of blood vessels to a tumor to provide nutrients as it grows

Question 11

What happens when tumor cells become invasive?

Answer 11

they enter the bloodstream and travel to distant sites within the organism

Question 12

What is an M1 event?

Answer 12

scenescence

a loss of proliferation

Question 13

What is an M2 event?

Answer 13

cells that were experimentally manipulated to lack p53 and pRb proteins
allowed for them to continue to proliferate for a finite amount of time in culture
also lack telomerase expression

Question 14

What conditions allow for cells to overcome crisis and continue to grow in culture indefinitely?

Answer 14

loss of p53 and pRb

presence of telomerase expression

Question 15

Describe the morphology of senescent cells.

Answer 15

huge, flat, “fried-egg” appearance, with large cytoplasm compared to nucleus
express acidic form of beta-galactosidase that is detected using colorimeric assay (blue stain)

Question 16

What is the difference between senescence and quiescence?

Answer 16

senescence is irreversible cell arrest whereas quiescence is regulated by growth factors, so it can be reversed by adding more

Question 17

What is triggered when the cell can no longer form t-loops to protect the end of the DNA in normal cells?

Answer 17

cell perceives these as DNA damage and activates p53 –> senescence in normal cells

Question 18

What is triggered when the cell can no longer form t-loops to protect the end of the DNA in cancer cells?

Answer 18

p53 is absent so cells will continue to proliferate and their telomeres will continue to shorten when telomeres disappear and cell loses coding capacity they undergo crisis

Question 19

What stimuli activate the p53 pathway?

Answer 19

telomere shortening

stress (e.g. sustained DNA damage that cannot be repaired, activation of specific oncogene pathways)

Question 20

Describe the methods cancer cells have used to maintain telomeres.

Answer 20

1. telomerase expression is re-activated (80% of cells)
2. telomerase-independent mechanism called ALT uses homologous driven recombination of the telomeric DNA (10-20% of cells)