Cancer Pathophysiology EXAM 1 Dr. Boessar Flashcards
What happens during G1 of the Cell cycle?
Preparation for DNA replication
the cell makes sure there is enough:
-nucleotides
-phosphate (for the ATP backbone)
-enough cellular energy
What regulates the G1-S interface checkpoint?
Rb protein (retinoblastoma)
-inactivation of this gene can lead to failure in regulating cell cycle progression -> cancer
Which enzyme allows the cell cycle to progress from G1 to the S-phase?
CDK (cyclin-dependent kinase) becomes phosphorylated and inactivates Rb
What happens in the S-Phase?
Synthesis and DNA replication (all 23 chromosomes)
Which protein induces apoptosis when replication errors occur?
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?
Which DNA repair enzyme corrects for single nucleotide (base) errors?
Base excision repair
PARP
Which DNA repair enzyme corrects for mismatch errors?
MSH2, MLH1
Which DNA repair enzyme corrects double strand breaks?
BRCA1 and BRCA2
What happens in the G2 phase?
Preparation of mitotic spindles (microtubules) for separation of the cells
What happens in the M-Phase?
Mitosis and cell division
What happens in the G0-Phase?
Quiescence or resting phase
What is the function of Oncogenes?
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…
What is the function of Tumor suppressor genes?
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)
What are viruses that can cause cancer?
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
Hallmarks of Cancer
-Sustained proliferative signaling
-Evading growth suppressors
-Resisting Cell death
-Inducing Angiogenesis (more blood production)
Name a concept of Sustained proliferative signaling
-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)
What is the function of PTEN?
What would happen if PTEN becomes mutated?
Growth suppression by inhibiting PI3K/AKT/mTOR pathway
mutation of PTEN can cause mutations
How does a mutation of c-myc oncogen cause mutations?
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
What is a way how cancerous cells resist apoptosis?
overexpression of Bcl-2
Bcl-2 blocks messenger proteins that cause apoptosis -> NO apoptosis
Which growth factor causes the growth of new blood vessels?
VGEF (vascular endothelial growth factor)
the cancer cell needs more blood flow (also glucose, oxygen, proteins, and a way to discharge waste)
A cancerous cell needs additional mutations to invade surrounding and distal tissues. T/F
True
How does a cancerous become immortal?
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
Why do telomer caps get shorter in healthy cells and undergo apoptosis after a certain number of cell cycles?
because older cells are more likely to have mutations
How do cancer cells “hide” from immune cells?
expression of PD-L1 preventing T-cell activation
How do cancer cells ensure sufficient energy supply?
upregulation of GLUT1 (glucose transporter)
(radioactive glucose is used in PET scans to make cancer cells visible)
Which inflammatory disease increases the risk for mutations?
GERD, Barret’s esophagus
chronic inflammation results in an increased supply of bioactive factors (growth factors -> more cell division -> higher risk for mutation)
What is phenotypic plasticity?
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)
What is nonmutational epigenetic reprogramming
no mutational changes
-changes in epigenetic gene regulation (ex: methylation), for example through hypoxia
How do bacteria affect cancer?
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
