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15 Cards in this Set
- Front
- Back
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What are the 6 "hallmarks of cancer"?
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1. Growth Factor independence (gain of f(x) oncogenes)
2. Loss of Responses to anti - growth signals and differentiated state (Loss of f(x) tumor suppressors) 3. Resistance to Apoptosis (inappropriate cell survival) 4. Limitless replicative potential (telomeres, DNA Damage responses) 5. Recruitment of blood/lymph (angiogenesis) 6. Invasion and Metastasis (cell shape, movement, colonization) |
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What are proto-oncogenes?
Oncogenes? |
Proto-Oncogenes: Normal genes with important roles in regulating division, differentiation, survival, and movement.
Oncogenes: Mutant counterparts, characterized by unregulated activity |
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What do oncogenes arise from?
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Arise from gain of f(x) mutation in proto-oncogenes
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Most proto-oncogenes have what function in the cell?
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Signaling
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Why can a single oncogene mutation have profound effects on cellular transformation?
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Because oncogenes typically encode proteins that regulate multiple downstream cellular responses
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What is PI3K?
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Oncogene pathways that is inappropriately activated in a large percentage of human cancers
- Kinase associated with intracellular signaling, phospharylates lipids - Converts PIP2 --> PIP3 |
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What is the function of PIP3?
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Extremely important organizational hub for cytoplasmic signaling
- Recruits impt proteins to plasma membrane that contain "pleckstrin homology" or PH domains |
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What is the primary downstream effector of PI3K?
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AKT, also referred to as Protein Kinase B (PKB)
PIP3 activates AKT AKT promotes cellular metabolism, cell growth, survival, and motility |
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What is a clinical consequence of activated AKT that deals with glucose?
- What does is produce? |
Activate AKT in cancer cells increases glucose transport and glycolysis
Produces the "Warburg Effect", the signature high glycolytic rate in many (but not all) human cancer cells |
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What specific mutation makes the PI3K/AKT pathway oncogenic?
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1. Overexpression and/or elevated activity
2. Decreased negative Regulation - loss of PTEN function (a phosphatase) |
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How do tumor suppressor genes cause cancer?
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By losing the activity via loss of function mutation
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What is the most commonly mutated tumor suppressor gene?
What is its normal function? |
p53 - can activate cell cycle arrest or apoptosis in cells exposed to many different stresses
- 50% of human tumors have inactivating mutations in p53 |
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What is Li-Fraumeni syndrome?
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Syndrome where patients have one germ line mutant copy of the p53 gene
- Classic example of loss of heterozygosity (LOH) |
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What type of protein is p53?
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DNA-binding transcription factor
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How is p53 negatively regulated?
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Transcribes its own negative regulator, MDM2, which targets p53 for degredation
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