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24 Cards in this Set
- Front
- Back
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are proto-oncogenes mutated?
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no they are not, an Oncogene is the mutated form
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what do growth associated proto-oncognes usually do?
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these usually induce synthesis of Cyclin D, forming the Cyclin D/CDK4/6 complex
(this hypophosphorlyates Rb, but alone is not enough to pass the restriction point) |
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What type of mutation typically affects oncogenes?
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this is usually a gain of function
only one mutated copy is required |
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What are the 3 ways that proto-oncogenes become oncogenes?
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Point mutations (hyperactive protein)
Gene Amplification (excess normal protein) Chromosomal Translocation (either excess normal protein or hyperactive protein) |
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How does Ras become active?
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Ras becomes active after Grb2, and GEF interact with it, this allows Ras to exchange a GDP for a GTP.
Eventually, Ras would hydrolyze the GTP back to GDP...ending the signal cascade |
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How does Ras become an oncogene?
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this causes Ras to lose the ability to hydrolyze GTP
This leads to constant signaling by Ras, this activates Raf even in the absences of growth signals |
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What does Raf do?
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this is activated by Ras (bound to GTP).
Raf then goes along and phosphorylates things in a cascade, leading to increased synthesis of growth related genes |
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What does MYC do in a normal cell? how does it become an oncogene?
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This is a transcription factor that stimulates expression of 15% of known genes
it becomes an oncogene NOT by mutation itself, but by over expression |
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what are two mechanisms to cause over expression of MYC?
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this can be caused by a chromosomal rearrangement, leading MYC to fall under a very active gene promoter
The MYC gene can become amplified, so that it is expressed in more than one chromosome |
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What happens in a cell with increased MYC?
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this will lead to excess transciption of growth associated genes
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What causes Burkitts Lymphoma?
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HIV or EBV infection leads to chromosomal translocation between Chromosomes 8 and 14 (in lymphocytes)
Results in MYC being placed near a very active promoter |
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What happens with the Philadelphia Chromosome?
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this is a translocation between chromosomes 9 and 22
results in a BCR-ABL hybrid which acts as an onocogene |
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What is the function of the proto-oncogene ABL?
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this is a tyrosine kinase activity protein
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What are the 3 phases of tumor development?
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Initiation
Promotion Progression |
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What happens in the initiation phase of tumor development?
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this is when a cell gains a mutation that has the Potential to give the cell a growth advantage
But normal cell cycle check points restrain the growth (ie only Ras mutated) |
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What happens during the promotion phase of tumor development?
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the cells with cancer potential are then exposed to agents which cause these cells (but not normal ones) to proliferate
Tumor promoters TEMPORARILY turn off cell cycle check points....removal of the promoter returns cells to normal |
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What happens during the progession phase of tumor development?
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This is the point where benign tumors become malignant, where compromised cells also lose the DNA checkpoints
This allows for unregulated growth in the ABSENCE of a tumor promoter (ie Ras and p53 both mutated) |
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What are the most common endogenous tumor promoters?
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Chronic inflammation
infection hormones |
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What aer the most common exogenous tumor promoters?
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booze
drugs tobacco smoke |
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What does cigarette smoke specifically do?
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this is a mutagen. it causes mutuations to occur
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what does alcohol specifically do?
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this is a tumor promoter, cause proliferation of cells
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What do tumors secrete to survive?
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VEGF (vascular endothelial growth factor)
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what defines a tumor as malignant?
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if it has broken through the basal lamina
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What allows tumor cells to pass through the basal lamina?
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malignant cells produce proteases called Matrix Metalloproteinases
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