Cancer Lectures Flashcards
How is cancer formed?
Normally, cells divide to a certain point, and generally they stop dividing if they are normal cells. But Cancer is from immortalized cells that just keep dividing and cause tumours. Formed from altered DNA/damaged DNA, causes damage in genes, gene expression etc.
When is a tumour most dangerous and results in death for a patient?
Patients die when the cancer has left the memory tissue and moved along, it is not the primary tumour that is the most dangerous but it is the metastatic tissue.
Cellular Transformation??? Go back and add.
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What is RSV?
RSV is a retrovirus that uses encoded enzymes (reverse transcriptase) to reverse transcribe their RNA genomes into complementary DNA (cDNA) which can then integrate into cellular genomes. It codes for its own reverse transcriptase, integrate into chromosomes of the cell that it infects and people use the retrovirus as a tool for genetic manipulation.
What is the difference between RSV and ALV? What did they discover?
- RSV contains an additional gene compared to other ALV, it is called src. It is based on the fact that it has a role in triggering the formation of sarcomas.
The sequence is critical for allowing the RSV virus to transform cells; without src, it would not do the job.
So they would look to see if src sequence was present or not.
They ended up finding src DNA sequence in both RSV-infected cells and unaffected cells. Now they dealt with the possibility that cellular genes may have a role in cancer.
Understand the slide: model for capture of src by ALV
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How does Src proteins function as tyrosine kinase? what is a kinase?
Kinase: an enzyme that removes a high-energy phosphate group from ATP and transfers it suitable protein substrate.
This was determine for Src using an anti-Src antibody experiment.
Phosphorylate specific Tyrosine amino acids in substrates. Can also phosphorylate itself (autophosphorylation).
Process:
You have Src and there is a catalytic cleft. And then there is a transfer of high-energy phosphate to kinase. ATP to ADP. Then there is a transfer of phosphate to substrate and the anti-Src antibody comes in.
What is the action of protein kinases and signalling?
- Kinases generally phosphorylate and thereby modify the functional state of substrate proteins.
- An example: AktPKB kinase influences multiple biological processes by phosphorylating a number of downstream substrates.
- Some of these processes are proliferation, angiogenesis, apoptoisis and protein synthesis.
- many but not all oncogenes are kinases.
- Many signalling cascades are effectively acting as readouts or information centres (from outside the cell) that are transferring to affect gene expression inside the cell.
Define Oncogene
A gene that increases the selective growth advantage of the cell in which it resides.
Define proto-oncogene
A normal gene that can become an oncogene as a result of mutations or increased expression.
Define tumour-supressor:
A gene that when inactivated or lost leads to an increase in selective growth advantage of the cell in which it resides.
What are the different ways to turn a proto-oncogene into a oncogene?
1) Amplification: a genetic alteration producing a large number of copies of a small segment of the genome.
2) Insertion/deletion (Indel): insertion or deletion of a few nucleotides.
3) Translocation: A specific type of rearrangement where regions of two non-homologous chromosomes are joined (e.g. Philadelphia chromosome).
4) Point Mutations: single-nucleotide substituions (e.g. A to G)
What is the difference between a driver mutation and a passenger mutation?
Driver mutation: a mutation that directly or indirectly confers a selective growth advantage to a cell.
Passenger mutation: a mutation that does not confer a selective growth advantage (“along for the ride”)
What is selective growth advantage?
It is the difference between birth and death rate in a cell population. Allows cancer cells to outgrow the surrounding ‘normal’ cells)
What is BCR-Abl?
It is an example of a cellular oncogene!
