Chapter 20 Flashcards
True or false: in one way or another, all diseases are related to our genetics in some way.
True.
What can be said about cancer in relation to genetics?
It is certainly linked to our genetics.
Define what a tumor is.
A tumor is the result of rapid cell growth compared to the nearby cells.
What is the difference between benign and malignant tumors?
Malignant tumor cells do NOT communicate properly with neighboring cells - they may travel in the blood to other tissues.
Benign tumor cells DO still communicate properly with other tissues, meaning they will stay where they are.
How are the cell cycles of normal cells different from those of tumor cells?
Normal cells have a balanced cell cycle with equal time spent in each phase, regulated by functional checkpoints.
Tumor cells, however, have shortened G1 and G2 phases due to defective checkpoints, a slightly longer but error-prone S phase, and often bypass G0, leading to continuous, unchecked proliferation.
What prevents cells from ‘wandering’?
Cadherin proteins are cell adhesion molecules that form junctions between cells that are the same type.
In regards to signal transduction, what do cadherins allow cells to do if say a liver cell linked to another by a cadherin bumps into a kidney cell?
It will allow cells to communicate with each other via signal transduction pathways to downregulate genes that contribute to proliferation - stop growth of cells in inappropriate places.
What is it called when a cell moves to another part of the body?
Metastasis
What happens to malignant cells in regards to other cells and their respective systems?
Malignant cells lose their ability to care about signals from other cells and they also oftentimes lose their ability to make proteins that keep them in their respective systems.
How does cancer kill you?
When cancer starts to affect an important organ; cells that normally keep you alive in these organs can get displaced by cancer cells.
In G1 and likely G2 and S phase, cyclins are _______________ made.
progressively
If the cell wanted to make a particular cyclin how would that happen?
RNA Polymerase would bind to the TATAA box up stream of the gene for the specific cyclin and after the mRNA is made it would need to be processed and then translated.
True or false: only a few cyclin are needed to progress into the cell cycle.
False, a lot of cyclins need to be made to have enough to bind to enough CDKs for progression to happen - it takes a little while for this to happen.
Take for example, cyclins being made during G1 to promote the progression of the cell into S phase.
What do the CDK’s do that are being turned on by these cyclins?
They are phosphorylating activators that will push the cell to make proteins that we will need during S-phase: DNA ligase, DNA poly, ss binding proteins etc.
In other words, the cell does not go into S phase and then decide to make proteins it needs for replication.
What are proto-oncogenes?
What is one mutation that could occur that won’t cause cancer?
What is one that could cause cancer?
They are genes whose products promote the forward movement of the cell cycle.
If the gene undergoes a mutation that makes it not work, that would not cause cancer.
If the gene undergoes a mutation that gives it a more stable half-life, that could cause cancer.
True or false: Mutations in proto-oncogenes always result in an oncogene.
False
When it is said that proto-oncogenes act in a dominant fashion, what does this mean?
Even if only one of the genes for a particular proto-oncogene becomes oncogenic, we have issues.
More progression than is normally granted will happen.
What are tumor suppressor genes?
They are genes whose protein products will slow or inhibit the cell cycle.
If a certain mutation of a tumor suppressor caused a lack of function within the protein product, would this be harmful?
Yes, any mutation that breaks or denatures the protein is no bueno.
When it is said that tumor suppressor genes are recessive, what does this mean?
What did we call this in cancer bio?
It means that both alleles for the gene must be mutated for it to be certainly harmful.
This idea is called Knudsen’s two hit hypothesis.
True or false: miRNA genes typically only act like proto-oncogenes.
False.
They can act as either proto-oncogenes or tumor suppressor genes.
What are mutator genes?
What would happen to other cancer genes without mutator genes?
They are genes whose protein product acts to repair damaged DNA.
Without these, tumor suppressors and proto-oncogenes would be more prone to mutations.
What is an example of a mutator gene that you can think of from Cancer Bio?
BRCA 1
ATM kinase
the genes involved in coding proteins involved in mismatch repair or otherwise
Explain the EGFR signalling pathway as it was described in cancer bio in the context of proto-oncogenes.
What are the possibilities of consequences that mutation could have on this pathway?
In response to a growth factor, the EGFRs will dimerize and auto-phosphorylate each other.
This creates docking sites for signalling molecules like Grb2, which bind to the EGFR intracellular domain via its own SH2 domain. Grb2 then recruits SOS, which will activate RAS by exchanging GTP for GDP.
Active Ras has a GTP bound to it. Ras has the ability to self regulate, but with the help of GAP it can do so more efficiently.
Active Ras will turn on the MAPK pathway on by activating Ras, Ras to Mek, Mek to MAPK.
As this is happening, Src protein is also recruited to the EGFR upon its activation, and acts to amplify and diversify the signal.
MAPK will then enter the nucleus and activate transcription factors for something like cyclins or E2F.
Mutations within this pathway can cause it to be “on all the time - constituent - and always turn genes involved in proliferation on even without a growth factor signal.
If you are born with a mutation (germline mutation) on one of your alleles for Rb, why would it be more likely for you to get a second hit vs. someone else how simply obtained a mutation on one of their alleles on a somatic cell?
There is just a much higher relative chance for you to get another mutation on the other allele if you have a germline mutation because that is in every cell.
It would be very unlikely for you to get another mutation on the same exact cell that obtained the mutation in the first place.
What is pRb?
This is the protein product of Rb gene.
What does pRb normally do?
It has the normal function of binding to E2F and preventing the progression of the cell cycle from G1 to S
What must happen to pRb so that it will “let go of” E2F?
It must be phosphorylated by a CDK
What does E2F do?
E2F is an activator that binds to enhancer sequences and mediator, thereby activating the genes associated with progression of the cell cycle to S phase.
Would E2F be considered an proto-oncogene or a tumor suppressor?
If it is able to bind to an enhancer sequence and mediator, it would be a proto-oncogene.
What would happen if someone was recessive for pRb?
It would mean that no functional pRb could be made, and that cells would have no way of preventing a G1 to S transition.
What does Mdm-2 normally do within the cell?
It normally stimulates the degradation of p-53 in the cell.
What happens when DNA damage is induced to the cell?
Both p-53 and Mdm-2 get phosphorylated.
This phosphorylation prevents Mdm-2s ability to bind, mark and degrade p-53, so we get an accumulation of it in the cell.
With p-53 now free to roam, what will it act as?
P-53 will act as an activator for various genes.
What safety mechanism that p-53 is involved in is listed as really good for when DNA damage happens?
P-53 will bind to an promoter region of the WAF1 gene, which will activate its transcription, leading to the mRNA that will be translated into P-21.
What does P-21 act to do within the cell?
It acts to bind to the Cyclin-CDK complex and prevent the CDK from phosphorylating pRb, giving the cell time to fix the mutation/damage.
Specifically CDK 4 and Cyclin D
What safety mechanism that p-53 is involved in is listed as pretty good for when DNA damage occurs?
p-53 will bind to a promoter region upstream of the gene for promiscuous DNA Poly, which will activate its transcription.
True or False: the gene for promiscuous DNA Polymerase could be deemed a mutator gene.
True
What does promiscuous DNA Poly do?
It helps to repair the DNA to an extent, even though it is not as accurate as the other polymerases.
ASK DR. C ABOUT THIS
What is the safety mechanism that involves p-53 is listed as poor?
This is when p-53 binds to a promoter for the gene Bax, thereby activating its transcription.
What is Bax responsible for?
Bax is responsible for binding to and neutralizing BCL2.
An inactive BCL2 will stimulate apoptosis.
What are BRCA-1 and
BRCA- 2 gene mutation associated with?
They are associated with an increased risk of breast cancer.
Women how have a germline mutation in these genes have a much higher rate of breast cancer and cervical cancer.
What is BRCA-1 gene involved with?
What will happen when there is no function of BRCA1?
It is involved with fixing DS breaks.
Without BRCA to assist in fixing DS breaks, there will be breaks in tumor suppressors, breaks in proto-oncogenes
