Cancer Pathophysiology EXAM 1 Dr. Boessar

Question 1

What happens during G1 of the Cell cycle?

Answer 1

Preparation for DNA replication

the cell makes sure there is enough:
-nucleotides
-phosphate (for the ATP backbone)
-enough cellular energy

Question 2

What regulates the G1-S interface checkpoint?

Answer 2

Rb protein (retinoblastoma)

-inactivation of this gene can lead to failure in regulating cell cycle progression -> cancer

Question 3

Which enzyme allows the cell cycle to progress from G1 to the S-phase?

Answer 3

CDK (cyclin-dependent kinase) becomes phosphorylated and inactivates Rb

Question 4

What happens in the S-Phase?

Answer 4

Synthesis and DNA replication (all 23 chromosomes)

Question 5

Which protein induces apoptosis when replication errors occur?

Answer 5

p53 (tumor suppressor gene, tp53 gene)

the more errors happen, the higher the concentration of p53 -> causes apoptosis (programmed cell death)

Which part of the cycle??
S-G2 Interface?

Question 6

Which DNA repair enzyme corrects for single nucleotide (base) errors?

Answer 6

Base excision repair

PARP

Question 7

Which DNA repair enzyme corrects for mismatch errors?

Answer 7

MSH2, MLH1

Question 8

Which DNA repair enzyme corrects double strand breaks?

Answer 8

BRCA1 and BRCA2

Question 9

What happens in the G2 phase?

Answer 9

Preparation of mitotic spindles (microtubules) for separation of the cells

Question 10

What happens in the M-Phase?

Answer 10

Mitosis and cell division

Question 11

What happens in the G0-Phase?

Answer 11

Quiescence or resting phase

Question 12

What is the function of Oncogenes?

Answer 12

a mutation to a protoncogene

Protoncogenes = genes that encode for proteins that make cells divide, if mutated they have increased activity or are activated all the time

EGFR (HER1)
HER2 (ERBb2, Neu, EGFR2)
CyclinD1
K-ras
N-ras
H-ras
Braf
Myc
Myb…

Question 13

What is the function of Tumor suppressor genes?

Answer 13

ensures proper progression through the cell cycle (brakes)

Tp53 (S-G2)
Rb (G1-S)
APC (often in colon cancer)
PTEN
BRCA1/BRCA2 (DNA repair gene)
NF1/NF2 (brain and spine tumors)
VHL (kidney cancer)

Question 14

What are viruses that can cause cancer?

Answer 14

Viruses hijack the cell and modify the genome -> risk of activating oncogenes or inactivation of a tumor suppressor gene

-HTLV-1-> T cell leukemia

-EBV (Epstein Bar virus) -> lymphoma

-HPV (Human papillomavirus) - cervical, oral, anal cancer)

-HBV/HCV (Hep B, C cause cancer through chronic inflammation due to more cell division)

-HHV (Humanes herpes virus)
-HIV

Question 15

Hallmarks of Cancer

Answer 15

-Sustained proliferative signaling
-Evading growth suppressors
-Resisting Cell death
-Inducing Angiogenesis (more blood production)

Question 16

Name a concept of Sustained proliferative signaling

Answer 16

-mutated growth factor receptors (always ON without binding of the growth factor EGF), usually controlled by tyrosine kinase

example: EGF pathway -> gene activation -> protein causes cell growth

-Stimulation of growth factors (autocrine (by the cell), paracrine (by nearby cells)

Question 17

What is the function of PTEN?
What would happen if PTEN becomes mutated?

Answer 17

Growth suppression by inhibiting PI3K/AKT/mTOR pathway

mutation can cause mutations

Question 18

How does a mutation of c-myc oncogen cause mutations?

Answer 18

c-myc is responsible for the differentiation of an adolescent cell to a mature cell -> adolescent cells have a higher potential to become cancer cells

Question 19

What is a way how cancerous cells resist apoptosis?

Answer 19

overexpression of Bcl-2

Bcl-2 blocks messenger proteins that cause apoptosis -> NO apoptosis

Question 20

Which growth factor causes the growth of new blood vessels?

Answer 20

VGEF (vascular endothelial growth factor)

the cancer cell needs more blood flow (also glucose, oxygen, proteins, and a way to discharge waste)

Question 21

A cancerous cell needs additional mutations to invade surrounding and distal tissues. T/F

Answer 21

True

Question 22

How does a cancerous become immortal?

Answer 22

The telomerase is adding Telomer to the Telomercap and thereby prevents apoptosis

the telomer cap of a normal cell would shorten after each cell cycle until it causes apoptosis

Question 23

Why do telomer caps get shorter in healthy cells and undergo apoptosis after a certain number of cell cycles?

Answer 23

because older cells are more likely to have mutations

Question 24

How do cancer cells “hide” from immune cells?

Answer 24

expression of PD-L1 preventing T-cell activation

Question 25

How do cancer cells ensure sufficient energy supply?

Answer 25

upregulation of GLUT1 (glucose transporter)

(radioactive glucose is used in PET scans to make cancer cells visible)

Question 26

Which inflammatory increases the risk for mutations?

Answer 26

GERD, Barret’s esophagus

chronic inflammation results in an increased supply of bioactive factors (growth factors -> more cell division -> higher risk for mutation)

Question 27

What is phenotypic plasticity?

Answer 27

atypical differentiation of progenitor cells

-Dedifferentiation (adolescent -> mature -> adolescent - adolescent are more likely to develop mutations)

-Blocked differentiation (stays adolescent)

-Transdifferentiation (Barret’s esophagus, squamous cells become columnar cells because of acid exposure)

Question 28

What is computational epigenetic reprogramming

Answer 28

no mutational changes

-changes in epigenetic gene regulation (ex: methylation), for example through hypoxia

Question 29

How do bacteria affect cancer?

Answer 29

polymorphic microbiome

-cancer-protective:
bacteria breakdown irritating molecules (ex alcohol)

-cancer-promoting:
bacterial toxins can damage host DNA
can cause inflammation (cancer risk)
can produce oncogenic metabolites (butyrate), if used by cells then more likely to develop mutations