Cancer (TSG, oncogenes) Flashcards
What does carcinos, carcinoma and oncos mean?
Carcinos = crab
Oncos = greek for swelling
Carcinoma → type of cancer that arises from epithelial cells
What theory about cancer was predominent around the 17th and 18 th centuries?
Infectious disease theory → cancer was infectious
Had separated hospitals for cancer patients and other patients
Now in modern days, what is know to cause cancer?
viruses, chemical carcinogens, radiation
What are the different acquired states of cancer cells?
GERESA DATI
IMPORTANT
1. Genome instability & mutation
2. Resitance to cell death
3. Sustained proliferative signaling
4. Evasion of growth suppressors
5. Enabling replicative immortality
6. Activating invasion & metastasis
NOT SO IMPORTANT
1. Avoiding immune destruction
2. Deregulation of cellular energetics
3. Tumor-promoting inflammation
4. Inducing angiogenesis
What was Peyton Rous’ study on?
On avian sarcoma in chicken being infectious → carcinogen was a virus called Rous sarmcoma virus (RSV)
1. Filtered tumor homogenate with sand
2. Collected the filtrate
3. Injected the filtrate → new tumors in healthy chickens
Conclusion: small quatities of cell-free filtrate have sufficed to transmit the growth to susceptible fowls (chickens)
What is the difference between cancer cells and normal cells when cultured in a Petri dish?
Normal cells stop dividing when they enter in contact → form a monolayer
Cancer cells/transformated cells → continue growing on top of each other → form a focus
Are transformed cells and tumors the same?
No, transformed cells can form tumours in the right conditions
What are the characteristics of a transformed cell? (7)
GGFLAMIT
1. Immortalization (not all immortalized cells are transformed)
2. Altered morphology (round shape)
3. Loss of contact inhibition (ability to grow over one another)
4. Anchorage-independent growth (growing without attachement to solid substrate, will grow in Jello)
5. Reduced requirement for growth factors
6. Increased transport of glucose
7. Tumorgenicity
How does a PET scan work?
Glucose is overly picked up by tumor cells
Inject radiolabelled glucose → picked up by tumor cells → positron-emission tomography (FGD-PET)
Makes it possible to visualize tumors in the body that have concentrated large amount of glucose
What is an example of cancer that virus driven?
HPV
What is a retrovirus? Give an example.
RSV is an example of a cancerous retrovirus
Use encoded enzyme (reverse transcriptase) to reversibly transcribe their RNA genome into complementary DNA (cDNA) which can then integrate into cellular genomes
Has the folowing coding regions:
- gag (core protein)
- pol (reverse transcriptase and integrase)
- env (envelope protein)
What charactertistic of RSV makes it a cancerous retrovirus compared to normal retroviruses?
Contains addition gene → src → has a role in triggering formation of sarcomas
Is src restricted to cancer cells?
No, found in DNA sequences in both RSV-infected and uninfected cells
c-src = proto-oncogene (in normal cells)
v-src = oncogene (viral gene)
dsDNA provirus (viral genome) → accidental integration next to c-src → co-transcription of viral and c-src sequences → fused ALV-src RNA trascript → packaging into capsid RSV virion carrying src sequences
*src = kinase
What are examples of oncogenes present in non-virally induced human tumours?
- abl
- erbB
- raf
- H-ras9
- K-ras9
- myc^i
What is the Src protein function?
Tyrosine kinase → phosphorylates speciifc Tyrosines in substrates
Src can also autophosphorylate
What is a kinase?
An enzyme that removes high-energy phosphate group from ATP and transfers it to a suitable protein substrate
By phosphorylating their substrates they change the functioanl state of the substrates
Kinases were determined frost for Src using anti-Src Ab that where phosphorylated after contact with Src
Many oncogenes are kinases
What are the effects of protein kinases signaling?
Gene transcription (which causes):
- proliferation
- angiogenesis
- apoptosis
- protein synthesis
What is the definition of an oncogene?
What is the definition of a proto-oncogene?
An oncogene is a gene that increases the selective growth advantage of the cell in which it resides
A proto-oncogene is a normal gene that can become an oncogene as a result of mutations or increased expression
*Gas pedals
What is a tumor-supressor?
A tumor-supressor is a gene that, when inactivated or lost, leads to an increase in the selective growth advantage of the cell in which it resides
*Its the brake pedal
What is a selective growth advantage?
The difference between birth rate and death rate in a population (of cells for oncogenes)
It allows cancer cells to outgrow the surrounding «normal» cells
How can a proto-oncogene turn into an oncogene?
- Amplification → Genetic alteration producing a lare number of copies of a small segment of the genome (more mRNAs)
- Insertion/deletion (Indel) → of a few nucleotides
- Translocation → Specific type of rearrangement where regions of 2 nonhomologous chromosomes are joined (ex: Philadelphia chromosome)
- Point mutations → single nucleotide substitution (can cause insertion of stop codons)
*These can happen in healthy individual and will not automatically cause cancer
What are Driver and Passenger mutations?
Driver mutation → direclty or indireclty confers a selective growth advantage to a cell
Passenger mutation → does not confer selective growth advantage
How does tumor mutation burden vary?
Some cancers have a much higher mutation burden, does not mean that all the mutations are driver mutations
Ex: Breast cancer has a low relative mutation burden compared to melanoma
What are examples of cellular oncogenes that were studied?
- BCR-Abl
- erbB2/HER2
- Ras