Neoplasia Flashcards
Senescent cells express which molecule?
SAGB
Senescence associated beta-galaxtosidase
What is the major inhibitor of autophagy?
mTOR
Chromosomal abnormality in 1/4 canine lymphomas
Trisomy of chromosome 13
Which gene mutation is associated with Hereditary Nodular Dermofibrosis and renal cystadenocarcinoma
BHD gene
Major types of epi genetic alteration
DNA Cytosine methylation
Histone modification
Cell cycle stage when RB is Phosphorylated
Inactive RB
Cell can proceed through G1/S transition
Cell cycle stage when RB is Hypophosphorylated
RB is active
Cell is quiescent
Hyperphosphorylated RB is
Active/Inactive
Inactive
Hypophosphorylated RB is
Active/Inactive
Active
Effect of active RB on cell cycle
Inhibits cell cycle progression
Effect of inactive RB on cell cycle
Cell cycle can proceed
Loss of heterozygosity
Loss of remaining normal tumor suppressor gene so only mutant remains
Haploinsufficiency
Inactivation of one allele is enough to allow tumor growth (some genes)
How does cancer cell metabolism change?
Switches to aerobic glycolysis
“Warburg Effect”
What inhibits PI3K
PTEN
What does CDK4-D Cyclin do?
Phosphorylates RB -> cell cycle progresses through G1 restriction
What induces p21?
P53
What induces P27
Growth suppressors
Eg. TGF-B
What induced p21 and what is the effect?
P53
Blocks cell cycle by binding to Cyclin-CDK complexes
What does p16/INK4a do?
Binds Cyclin D-CDK4 prevents phosphorylation of RB -> cell cycle stopped
What does p14/ARF do?
Inhibits MDM2 -> Increases p53
P53 acts through which molecule to stop the cell cycle?
P21
APC function
Inhibits WNT signalling
NF1 function
Inhibits RAS/MAPK signalling
NF2 function
Cytoskeleton stability
Hippo pathway signalling
PTCH function
Inhibits Hedgehog signalling
PTEN function
Inhibits PI3K/AKT signalling
SMAD2 & 4 function
TGF-B signalling pathway:
Inhibits MYC & CDK4
Induces CDK inhibitors
Key cell cycle regulators that are commonly mutated in neoplastic cells
RB
Cyclin D
P21
CDK4
MDM2 function
Degrades p53
Which molecule causes scirrhous reaction in tumors?
PDGF
What Cyclin complexes regulate the G1-S transition?
CDK4-Cyclin D
CDK6-Cyclin D
CDK2-Cyclin E
Which Cyclin complexes are active during S phase?
CDK1&2-Cyclin A
Which Cyclin complex is active during the G2-M transition
CDK1-Cyclin B
Inhibitors of CDK4 & 6 - Cyclin D complexes
INK4 Inhibitors: P15 P16 P18 P19
Inhibitors of all CDKs
P21
P27
P57
Molecules that sense DNA damage and their effect
ATM & ATR
Inactivate MDM2 -> increase p53
Keg molecule affected by loss-of-function mutations in VHF
HIF1-a
Receptor Tyrosine Kinases inactivate which molecule to alter metabolism in neoplastic cells & effect
M2 Isoform of pyruvate kinase
Dams pathway -> intermediates for macromolecule synthesis
FLIP
Protein that binds to death-induced signalling complex -> prevents Caspase 8 activation
Anti-apoptosic molecules upregulated in neoplastic cells
BCL-2
BCL-XL
MCL-1
Main proteases for tumor invasion
MMP
Cathepsin D
Urokinase plasminogen activator
Genetic alteration in canine mast cell tumors
Internal tandem duplication of c-kit gene
Gene mutated by aflatoxin B1
P53
Characteristic of DNA mismatch repair defects
Microsatellite instability
PP2A function
Tumor suppressor that negatively regulates RAF, MEK (both downstream of RAS) and AKT
LKB1 function
Epithelial protein for contact inhibition
Loss= cells are susceptible to MYC induced carcinogenesis
Which molecule is upregulated in neoplastic cells to support energy demands of aerobic glycolysis?
GLU1
- glucose transporter
