Exam 2: PollEv Questions

Question 1

Which CDK and cyclin do you predict to be important during the R check point?

Answer 1

CDK 4/6

Question 2

Which version of RB is present at the stage labelled 1-6?

Answer 2

• dephosphorylated
• monophosphorylated
• hyperphosphorylated
• hyper
• hyper
• hyper

Question 3

Which version of the retinoblastoma protein causes progression past the R checkpoint?

Answer 3

Hyperphosphorylated

Question 4

Which of the following statements is true regarding MYC dysregulation?
A) MYC/MAX complexes inhibit the transcription of p15 (an inhibitor of CyclinD2-CDK4), thus promoting cell cycle progression through G1.
B) MYC/MAX complexes promote the transcription of CyclinD2-CDK4, thus promoting cell cycle progression through G1.
C) MYC/MAX complexes inhibit the transcription of E2F transcription factors, thus promoting transition through the R checkpoint.
D) MYC/MIZ-1 complexes activate the txn of p15 (an inhibitor of CyclinD2-CDK4), thus promoting cell cycle progression through G1

Answer 4

B) MYC/MAX complexes promote the transcription of CyclinD2-CDK4, thus promoting cell cycle progression through G1.

Question 5

1) Which color genes are classical proto-oncogenes in the figure to the right?
2) If a proto-oncogene in this pathway is activated in a cell what would be the final effect?
(Ch. 8 Part 2, slide 18)

Answer 5

1.) red
2.) transcription past the R-checkpoint (cell division)

Question 6

Cells were exposed to TGF-B forgiven times.
* Levels of p15 mRNA were
measured.
* What does this data suggest?
A) Active TGFB signaling has no effect on p15 mRNA.
* B) Active TGFB signaling inhibits degradation of p15 protein.
* C) Active TGFB signaling causes increased translation of p15.
* D) Active TGFB signaling induces transcription of p15.

Answer 6

D. Active TGFB signaling induces transcription of p15

Question 7

What statement best describes apoptosis?
A) Apoptosis is mediated through a
protein called TP53.
* B) All cells have the ability to initiate
apoptosis at any given time.
* C) Apoptosis ensures overall health and
viability of an organism.
* D) All of the above

Answer 7

D) all of the above

Question 8

What would you expect if a
cell has 1 copy of a TP53
mutant allele with a point
mutation? (Ch. 9, Slide 8)
A- The cell would have almost no TP53 function.
B- The cell would have almost
normal TP53 function.
C- The cell would have 1/2 of the normal TP53 function.
D- The cell would have double
the normal TP53 function.

Answer 8

A) The cell would have almost no TP53 function

Question 9

What would you expect if a cell has 1 copy of a TP53 mutant allele that generates a null allele (complete loss of the protein)? (Ch. 9, Slide 8)
A- The cell would have almost no TP53 function.
B- The cell would have almost
normal TP53 function.
C- The cell would have 1/2 of the normal TP53 function.
D- The cell would have double the normal TP53 function

Answer 9

B- The cell would have almost
normal TP53 function

Question 10

Cells from mice with different TP53 genotypes were treated with X- irradiation (induces DNA damage) (Ch. 9, slide 13)
* What does this data argue?
* A) TP53 is required for cell death in response to DNA damage.
* B) Loss of TP53 is required for cell death in response to DNA damage.
* C) TP53 protein levels decrease in response to DNA damage.
* D) TP53 protein levels increase in response to DNA damage.

Answer 10

A) TP53 is required for cell death in response to DNA damage.

Question 11

Is MDM2 a tumor suppressor gene or proto-oncogene?

Answer 11

proto-oncogene

Question 12

If cells have lost proper control of RB, and have high levels of E2F activity, what would you expect to happen based on the above pathway?

Answer 12

If RB is not functioning properly, E2F is left uninhibited so the transcription of ARF is constitutively active and MDM2 will not be negatively regulated -> TP53 levels increase -> apoptosis

Question 13

Adult endometrial fibroblasts were continually passaged in culture.
* They stopped growing after ~43 population doublings.
* CDK inhibitors p21 and p16 increase as cells approach replicative senescence.
* How does this compare to senescence in HMEC (our 2nd JC paper)?

Answer 13

it is similar to HMEC cells because p16 is increased but different in that p21 is not involved in HMEC

Question 14

Which of the following statements is true regarding TP53 (p53)?
* a- It is an oncogene, and can cause transformation when upregulated.
* b- TP53 functions as a dimer meaning two subunits can come from different TP53
alleles.
* c- When a cell undergoes physiological stress it causes upregulation of TP53
transcription.
* d- When a cell undergoes physiological stress it causes inhibition of the degradation
of TP53 protein

Answer 14

d- When a cell undergoes physiological stress it causes inhibition of the degradation
of TP53 protein

Question 15

What organelle do you think holds the molecular controls that can activate apoptosis?

Answer 15

mitochondria

Question 16

1) What is happening here?
A- increased apoptosis.
B- decreased apoptosis.
C- normal apoptosis.
2) What is happening here?
A- increased apoptosis.
B- decreased apoptosis.
C- normal apoptosis.
(ch.9 part 2, slide 16)

Answer 16

1. A
2. C

Question 17

Select 1 protein in the pathway to the right and describe how either
activation or inhibition can lead inhibition of apoptosis in a cancer cell. (3 pts)
(ch. 9 part 2, slide 31)

Answer 17

• Inhibition of TP53 (1 pt, accurately selecting a
  molecule and inhibition or activation)
• PUMA and BAX normally create pores in the mitochondrial membrane which allows cytochrome-c escape and activation of
  apoptosis. (1 pt, description of normal mechanism)
• Inhibition of TP53 in a cancer cell would cause a decrease in the transcription of PUMA and BAX. Downregulation of PUMA
  and BAX in a cancer cell would inhibit pore formation in the mitochondria and apoptosis
  would not be able to occur. (1 pt, description of how altered mechanism would contribute
  to inhibition of apoptosis)

Question 18

2) Which of the following is true about TP53?
* A- It can induce apoptosis via initiating transcription of a death receptor.
* B- It can induce apoptosis via
upregulation of pro-apoptotic proteins that induce mitochondrial pore formation.
* C- It can induce the transcription of DNA repair proteins.
* D- It can induce senescence.
* E- All of the above

Answer 18

E- all of the above

Question 19

What do you predict would
happen to this chromosome if cell division proceeded?
(ch. 10, slide 25)

Answer 19

The attached sister chromatids would be torn apart during anaphase,
and not at the original point of ligation, just in a random location
- This process of chromosomal breakage and fusion will repeat: breakage-fusion-breakage cycles.

Question 20

Which of the following events would result in an immortal human cell?
* A) activation of telomerase
* B) Inactivation of p16 and inactivation of TP53
* C) Inactivation of p16 and activation of telomerase
* D) Inactivation of p16 and inactivation of telomerase

Answer 20

C) Inactivation of p16 and activation of telomerase

Question 21

If you knocked out both copies of mTR (the mouse telomerase RNA gene) and essentially inhibited telomerase activity in all cells of a mouse. What would you predict would happen to that mouse?

Answer 21

In mice- not much will change. Telomere length does shorten but mice have really long telomeres so they aren’t affected

Question 22

Why is it a large smear? What does this suggest? (TRF) (Ch. 10, part 2, slide 15)

Answer 22

It looks like a large smear because the chromosomes are not all the same length, suggesting that not every telomere in a cell is the same length and same cell types do not produce telomeres of the same length

Question 23

Why do the products show up as a ladder? What does this suggest? (TRAP) (Ch. 10, part 2, slide 17)

Answer 23

telomerase adds more telomeric sequences to the end (adds 6 bases) creating the appearance of a ladder.

Question 24

Journal Club 3 Figure 1:
What statement below is something that Figure 1 directly shows?
A) p16 is required for the stasis senescence barrier and
inactivation of p16 is sufficient
for all cells to bypass the stasis senescence barrier.
* B) Genomic instability is not
necessary for barrier bypass.
* C) MYC causes an increase in telomerase activity

Answer 24

A) p16 is required for the stasis senescence barrier and
inactivation of p16 is sufficient
for all cells to bypass the stasis senescence barrier.

Question 25

Journal Club 3 Figure 1:
Which experiment shows
this the best?
* A) p16shRNA in cells grown in M85.
* B) BaP treatment in cells grown in MM.
* C) No treatment in cells grown in MCDB170.

Answer 25

A) p16shRNA in cells grown in M85.

Question 26

Journal Club 3 Figure 2:
What statement below is
something that Figure 2
directly shows?
* A) Genomic instability is not
necessary for barrier bypass.
* B) MYC causes an increase in telomerase activity.

Answer 26

B) MYC causes an increase in telomerase activity.

Question 27

Journal Club 3 Figure 2:
Which experiment shows
this the best?
A) MYC added to post-stasis
p16shRNA cells grown in M85.
* B) MYC added to BaP treated in cells grown in MM.
* C) MYC added to cells grown in MCDB170

Answer 27

A) MYC added to post-stasis
p16shRNA cells grown in M85?

Question 28

Journal Club 3 Figure 3:
What statement below is
something that Figure 3
directly shows?
* A) Inactivation of p16 is required for bypass of the first senescence barrier.
* B) MYC causes an increase in telomerase activity.
* C) Genomic instability is not
necessary for immortalization of HMEC.

Answer 28

C) Genomic instability is not
necessary for immortalization of HMEC.

Question 29

Journal Club 3 Figure 3:
Which cell line shows this
the best?
* A) MYC added to post-stasis
p16shRNA cells grown in M85.
* B) MYC added to BaP treated in cells grown in MM.
* C) MYC added to cells grown in MCDB170.

Answer 29

A) MYC added to post-stasis
p16shRNA cells grown in M85

Question 30

Journal Club 3 Figure 4:
What statement below is something that Figure 4 suggests?
* A) MYC likely causes an increase in telomerase activity.
* B) MYC likely causes an increase in hTERT transcription.
* C) The immortalization process likely does not involve a change in the chromatin
state surrounding the hTERT gene.

Answer 30

C) The immortalization process likely does not involve a change in the chromatin
state surrounding the hTERT gene.

Question 31

How long do you think it generally takes for a cancer to form?
* A- 0-1 years
* B- 2-5 years
* C- 5-10 years
* D- 20-40 years

Answer 31

D- 20-40 years

Question 32

(Ch. 11, slide 16)
Which statement is true?
* A) Colon cancers typically take 5-20 years to form.
* B) The hyperplastic state of cervix cancer is referred to as CIN3.
* C) Regarding breast cancer progression, it takes 6-10 years for a benign tumor to become cancer.

Answer 32

C) Regarding breast cancer progression, it takes 6-10 years for a benign tumor to become cancer.

Question 33

(Ch. 11, slide 25)
Which combination of mutations will result in
colon carcinomas?
* A) AXIN2, B-raf, SMAD4, and TP53
* B) AXIN2, B-raf, TGFBRII, and TP53
* C) AXIN2, B-cat, APC, WTX
* D) AXIN2, B-cat, SMAD4, and TP53

Answer 33

A) AXIN2, B-raf, SMAD4, and TP53

Question 34

(Ch. 11, slide 36)
Which statement is accurate about the following figure?
* A) MYC mutations cause
tumorigenesis more quickly than RAS mutations.
* B) All mice with MYC mutations remain tumor-free.
* C) All mice with RAS mutations remain tumor-free.
* D) Mutations in RAS and MYC have an additive effect on mammary tumorigenesis.

Answer 34

D) Mutations in RAS and MYC have an additive effect on mammary tumorigenesis.

Question 35

Are all cells within a tumor more likely genetically identical or different? Why?
* A) identical; genomes are more unstable at the early stages of progression
* B) different; genomes are more unstable at the early stages of progression
* C) identical; genomes are more unstable at the later stages of progression
* D) different; genomes are more unstable at the later stages of progression

Answer 35

C) identical; genomes are more unstable at the later stages of progression

Question 36

Cancer Stem cell theory (side 41)

Answer 36

• Observations:
• Only 1% of the cells in a leukemia were tumorigenic (able to form a new tumor
  when injected in a mouse)
• Only 2% of the cells in a breast tumor were tumorigenic
• The different cell populations did not differ genetically.
• Interpretation:
• Cancer stem cells- tumors contain subset of cells that can self-renew and generate countless progeny to produce
  a new tumor.
• Although stem cells and differentiated cells have same genome, the differentiated cells have lost their tumor initiating abilities.

Breast tumor cells
* Green cells- lower in number, able to form a tumor in a mouse
* Blue cells- higher in number, not able to form a tumor in a mouse

Question 37

Peto’s Paradox

Answer 37

• Larger animals are composed of more cells than smaller animals
• Larger animals undergo more cell divisions than smaller animals
• Animals that have longer lifespans have more cell divisions
• Cell divisions give rise to mutations, due to errors in mitosis
• Therefore, larger animals and animals with longer lifespans should get more cancer than smaller animals
• BUT they don’t!
• = Peto’s paradox

Question 38

Human vs mouse cells resistance to immortalization

Answer 38

• Mouse cells grown in culture will spontaneously immortalize relatively easily.
• Human cells, rarely, if ever, will spontaneously immortalize in culture.
• Because mouse cells readily express telomerase and human cells do not

Question 39

Human cells need _____ mutations to confer
transformation

Answer 39

• more
• Small rodents only need mutations in 2 genes to be capable of tumorigenesis
• Large rodents and humans need mutations in least 5 genes to be capable of
  tumorigenesis
• Hypothesis: Animals with increased body size and longer lifespans have evolved more
  anti-cancer mechanisms to prolong cancer formation

Question 40

What are some potential processes that cause our DNA sequence to change (mutate)?
* A- errors in DNA replication
* B- exposure to endogenous mutagens, (Reactive oxygen species- cell respiration)
* C- exposure to exogenous mutagens (UV exposure- sun)
* D- All of the above

Answer 40

D. All of the above

Question 41

Which cells are the most important to protect
from becoming transformed?
* A) Stem cells
* B) Transit-amplifying cells
* C) Differentiated cells

Answer 41

A) Stem Cells

Question 42

(Ch. 12, slide 23)
D400A Survival curve: What does the figure show?

Answer 42

Percent survival decreases with age for that with D400A/D400A. Percent survival remains relatively the same for those with +/+ and +/D400A.

Question 43

Do you think DNA repair enzymes ….?
* A) are tumor suppressor genes and act recessively; you need both copies to lose function to get increased cancer risk.
* B) are proto-oncogenes and act dominantly; you only need 1 gain-of- function mutation to get increased cancer risk.

Answer 43

A) are tumor suppressor genes and act recessively; you need both copies to lose function to get increased cancer risk.

Question 44

What is the definition of a
double-stranded break in DNA?

Answer 44

when a sugar-phosphate bond is broken in both strands of DNA. Resulting in a physical breaking apart of 1 DNA molecule into 2 separate DNA molecules.

Question 45

JC 4, figure 1
You treat cells with an agent that
induces DNA damage and then
label BRCA1 using an anti-BRCA1
antibody. Which result do you
expect to see using the images on the right.
* A) Cells that look like A
* B) Cells that look like B
* C) Cells that look like both A and B
* D) Cell that look like neither A nor B

Answer 45

A) Cells that look like A

Question 46

JC 4, figure 2
Which of the following statements if true regarding the dynamics of BRCA1 protein?
* A) BRCA1 accumulates at high levels at G1 phase
* B) BRCA1 is phosphorylated at G1 phase
* C) BRCA1 is not phosphorylated at S phase
* D) BRCA1 is phosphorylated in the presence of DNA damage
* E) Both C and D

Answer 46

D) BRCA1 is phosphorylated in the presence of DNA damage

Question 47

JC 4, figure 3
Which cell image on the right
corresponds to the data point
circled in the image below?
* A) A
* B) B
* C) Both
* D) Neither

Answer 47

B) B

Question 48

JC 4, figure 5
Which statement is the most accurate interpretation of Figure 5:
* A) When DNA is replicated, BRCA1 localizes to sites of replication.
* B) When DNA is replicated, BRCA1 localizes to sites of double-stranded breaks in
DNA replication forks.
* C) When DNA is damaged, BRCA1 localizes to sites of replication.
* D) When DNA is damaged, BRCA1 localizes to sites of double-stranded breaks in DNA replication forks.

Answer 48

D) When DNA is damaged, BRCA1 localizes to sites of double-stranded breaks in DNA replication forks.