Ras signaling Correct Answers - GTPase
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- promotes growth and proliferation
- mutated in 20-30% of all cancers
- point mutations are most common
G12V mutation Correct Answers - blocks GAP binding
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- locks RAS in active state, promoting proliferation
Q61K mutation Correct Answers - raises activation energy of
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GTP hydrolysis
- blocking hydrolysis, keeping RAS active
Hallmarks of cancer Correct Answers 1) self-sufficiency in
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growth signals
2) insensitivity to anti-growth signals
3) unstable DNA
4) metastasis
5) evasion of apoptosis
6) abnormal cellular metabolism
7) angiogenesis
8) inflammation
9) evasion of immune system
10) immortality
Anti-growth signals Correct Answers - can be internal or external
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- can be normal or induced
- must be overcame in normal cells to proliferate
p53 Correct Answers - damage sensor
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,- tumor suppressor gene
- halts cell cycle at G1 phase
- >50% of tumors contain mutation or deletion
R72P mutation Correct Answers - block DNA binding
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Rb Correct Answers - binds E2F (transcription factor) blocking
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transcription
- when phosphorylated it releases E2F allowing transcription
Rb mutations Correct Answers - mutated, present but unable to
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bind E2F
- downregulated, allows for further transcription
- CDK overactivity - allows for Rb to be phosphorylated
Unstable DNA Correct Answers - genetic instability
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- chromosomal instability
- enabling hallmark
- can cause drug resistance
Chromosomal instability Correct Answers - gain or loss of whole
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chromosomes
- can get double or quadruple genomes
- gain of pro-growth/invasive genes
- loss of growth inhibitory genes
Endoreduplication Correct Answers - replication without nuclear
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division
- failed cytokinesis
Multipolar spindles Correct Answers - monopolar spindle
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, - lagging chromosomes
Metastasis Correct Answers - cancer cells move into blood and
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relocate
- cause 90% of deaths from solid tumors
- 30-40% of newly diagnosed patients have detectable
metastases
- 20-30% of remaining patients are clinically free of metastases
harbor hidden metastases
Apoptosis Correct Answers - programmed cell death (suicide)
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- cell volume loss
- membrane blebbing
- formation of
- apoptotic bodies
- DNA fragmentation & condensation
- collapse of cytoskeleton
- immune cell engulfment
- non-inflammatory
Intrinsic apoptotic stimuli Correct Answers - DNA damage -
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senese by P53
- loss of survival hormones
- cell detachment from designated area (anoikis)
- radiation
- increased levels of oxidants
- chemo
Extrinsic apoptotic stimuli Correct Answers - death receptor
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death ligand binding
- expression of abnormal cell surface antigens