Cancer Flashcards
What cell types does cancer largely occur in?
somatic cells
Is cancer a disease?
no
rather, it is a family of related complex diseases
this is why there will never be any one cure for cancer
two fundamental properties of cancer
- unregulated cell proliferation
2. metastatic spread
How does cancer spread?
through the bloodstream
How does cancer occur?
the accumulation of many mutations
very rarely occurs from a single mutation
How can you determine if cancer in two different locations arose independently from one another or are from the same original tumor?
- compare base sequences in both areas
2. look for similar chromosomal irregularities in karyotype
Tasmanian devil facial tumor disease (DFTD) case
DFTD is a rare transmissible form of cancer
Due to eating together and violently clawing prey, tasmanian devils can transfer cancer through blood on their face
they also have little genetic diversity which gives rise to this
Mutation error rate
10^-6 mutations per gene in each division
How many mutations might a person have per gene in a lifetime?
10^10
Why does the risk of cancer increase with age?
acquire more mutations as more divisions take place and the risk of cancer increases
What happens if cyclins are never degraded?
CDK proteins will always be on and cell cycle will progress without control
this can lead to cancer
Retinoblastoma (RB) checkpoint protein
ensures that the cell passes from G1 to S only when ready
tumor supressor protein
what happens when RB is on?
the cell does not pass from G1 to S
how do you turn RB off? what happens when RB is turned off?
RB is phosphorylated to turn off by cyclin-CDK complexes
when RB is turned off, the cell is free to move into the S phase
How does RB work?
binds to transcription factor (E2F) that promotes gene expression and prevents it from transcribing certain genes
when RB is not bound to E2F, E2F allows certain genes to be expressed that further the cell from G1 to S
P53 checkpoint
evaluates DNA damage and can prevent its replication through stimulating the transcription of the Cdk inhibitor, p21
p21
inhibits Cdks from phosphorylating RB
this allows RB to stay turned on and the cell cycle does not progress from G1 to S
How many copies of the genes have to be mutated for tumor supressors to not work?
both copies
How many copies of the genes have to be mutated for proto-oncogenes to become oncogenes?
just one copy
Proto-oncogenes
genes whose products promote cell growth and division
Tumor supressor genes
when both alleles are mutated, cells can keep growing
Oncogene
proto-oncogene that has been mutated and can lead to uncontrolled cell growth/division
What do many oncogenes encode for?
constitutively active signal-transduction pathways
constitutively = enzyme/protein that is produced in constant amounts regardless of environmental conditions
ABL
gene on chromosome 9 that encodes a tyrosine kinase
BCR
gene on chromosome 22 that encodes an unknown protein
when in the Philadelphia chromosome, provides a docking site for signal transduction proteins
BCR-ABL translocation (gives rise to the Philadelphia Chromosome)
oncogene caused by fusing of ABL and BCR genes
encodes for a cytosolic nonreceptor kinase
can phosphorylate some substrates that are not normal targets
What happens if the BCR-ABL translocation occurs in the blood forming cells of the bone marrow?
initial phase of chronic myelogenous leukemia (CML)
expansion of white blood cells
Imatinib (Gleevec)
binds directly to ABL kinase active site and inhibits kinase activity
What was Imatinib the first drug to do?
act upon a specific enzyme rather than non-specifically inhibiting and killing all dividing cells
What checkpoint does MPF regulate?
the G2 checkpoint
When do MPF concentrations peak?
partially through mitosis
How does the BCR-ABL protein differ from the normal ABL protein?
Normally, ABL kinase is regulated by other molecules, but the BCR-ABL mutant kinase is constantly active
