Revision of Cancer Biology Flashcards
what are the 6 hallmarks of cancer cells
- Growth signals are not required for cell survival, growth and differentiation
- unresponsiveness to growth-inhibitor signals
- evasion of apoptosis
- defects in DNA repair
- limitless reproduction potential
- ability to invade and metastasis
- angiogenesis (blood vessel formation) is sustained and increased
what is angiogenesis
blood vessel formation
What is a pro-oncogene
a normal gene from which an oncogene is derived when mutated, it has the potential to transform a cell into a cancerous state – cacner results when activated GAIN OF FUNCTION
What is an oncogene
gene that encodes protein capable of inducing cancer, activated by gain of function
Give some examples of an oncogene
BCL-2, C-MYC, VEGF, TGF alpha, EGFR, VEGFR, B-Raf
What cancers does EGFR over expression cause
- Colorectal cancer
- Pancreatic cancer
- Lung cancer
- non-small cell lung cancer
what cancer does Ras mutation cause
- Pancreatic cancer
- Papillary thyroid cancer
- Colon cancer
- Non-small cell lung cancer
What cancer does EGFR mutations cause
- NSCLC
- Glioblastoma
What cancer does B-Raf mutation cause
- Melanoma
- Papillary thyroid cancer
- Colon cancer
What is a tumour suppressor gene
- Tumour suppressor genes mainly act to block development of cancer, allows the cell to stop and carry on in the cell cycle
How do tumour suppressor genes become cancerous
loss of function
what are the 3 types of tumour suppressor gene classes
- Gatekeeper
- caretaker
- pro-apoptotic
Give some examples of the three types of tumour suppressor gene classes
Gatekeeper
- p54
- pRB
caretaker
- BRCA (1/2)
- MMR( mismatch repair gene)
pro-apoptotic
- Bax
How do tumour suppressor genes restrict cell life proliferation
- Control the cell cycle and cell division
- Induce apoptosis when other mechanisms have failed
what causes angiogenesis in cancer cells
vascular endothelial growth factor which can be released by cancer cells
give an example of photo-oncogenes and what cancers they cause
- Translocation = t(14;18)(q32;q21) Bcl-2= follicular lymphoma
- Amplification in ERBB2 or HER2 breast cancer
- c-Fos (transcription factor)Skin/endometrial = point mtuations
- c-H-ras (Gly)GGC- (Val)CTG = bladder = point mtuations
What does a gatekeeper tumour suppressor gene do
regulate entry into the cell cycle and the cell cycle
What does a pro-apoptotic tumour suppressor gene do
- causes apoptosis
- if there is a mutation in pro-apoptotic tumour suppressor gene this means that apoptosis is inhibited therefore this can lead to immortality of the cells
Name the main types of DNA damage that can happen
Single strange breaks (spontaneous mutations)
Damage DNA bases – cause of mismatch errors
UV light
Replication errors
Interstrand breaks within the DNA
Describes examples of
- Single strange breaks (spontaneous mutations)
- Damage DNA bases – cause of mismatch errors
- UV light
- Replication errors
- Interstrand breaks within the DNA
Single strange breaks (spontaneous mutations)
- reactive oxygen species
- x rays
- oxygen radicals
- spontaneous reactions
Damage DNA bases – cause of mismatch errors
- alkylating agents (usually methylation)
UV light
- UV light
- Causes the Addiction of bulky adducts
- Or causes pyrimidine dimers
- Polycyclic hydrocarbons – see from tobacco smoke
- Specific DNA remair mechanism within the cell to repair this
Replication errors
- Replication errors such as depurination
- Occur normally during the cell cycle s, G1, and G2 phases
Interstrand breaks within the DNA
- UV lights
- Hydroxyurea
- X rays
- Anti -tumour agents
describe the features of benign tumours
- Generally slow growing but progressive.
- Mitotic figures rare - this is the ability to see cells going through mitosis on the slide
- Non-invasive
- Non- metastasising.
- Well differentiated.
Describe the features of malignant tumours
- Fast growing
- Mitotic figures may be numerous and abnormal.
- May ulcerate on the surface
- Local invasion – clinical cardinal feature
- May metastasise –cardinal clinical feature.
- More common with large undifferentiated primary tumours
- May see weight loss, anorexia and anaemia
What is the main clinical cardinal feature of malignant tumours
metastasises
Describe what the normal prostate gland look like
Tubuloalvolar glands
basal cells
describe what BPH looks like
- Crowded tubules
- columnar arrangement near gland
- nucleoli not typically seen
describe the difference between a high grade and low grade PIN - (Prostatic intraepithelial neoplasia)
Low grade PIN
- Nucleoli not prominent
- Tissue appears almost normal
- Intact basal layer
High grade PIN
- Large nuclei,
- hyperchromasia
- prominent nucleoli,
- scattered basal cells periphery
What does a malignant prostate gland look like
- note size of nucleus: cytoplasm = high nuclei to cytoplasm ratio
- prominent nucleoli
- absence of basal cell layer
- hyperchromasia
What are the common sites of metastases for breast
bone and lung and liver
What are the common sites of metastases for ovarian
liver
what are the common sites of metastasis for pancreas
liver and lung
what are the common sites of metastasis for lung
- adrenal gland
- bone
where are the common sites of metastasis for colon
liver
What does a mesenchymal cell phenotype allow the tumour to do
- enhanced migratory capacity
- invasiveness
- elevated resistance to apoptosis
- > ECM components.
What is a epithelial cell polarised
-when the basement membrane is on the basal surface
What is MAT(mesenchymal–amoeboid transition)
the acquisition of amoeboid motility by mesenchymal cells is often associated with enhanced metastasis.
what are the two types of changes that cancer cells undergo in order to allow them to metastasise
epithelial cells to mesenchymal amoeboid cell - this means that they have an enhanced ameboid movement and metastasis
the cell loses epithelial characteristic and gains a mesenchymal – start to produce proteases so they can pass through the basement membrane and enter the blood stream
what can be used as an early marker of cancer
the cell loses epithelial characteristic and gains a mesenchymal – start to produce proteases so they can pass through the basement membrane and enter the blood stream = this can be an early marker of cancer
what are the 4 main phases of the cell cycle
- G1
- S
- G2
- M
- GO – non dividing, fully differentiated or quiescent stem cells, or not going through the cell cycle
How long does each part of the cell cycle take
- 23 hours spent in interphase
- 1 hour spent in mitosis
what is interphase made up of
G1
GO
S
G2
what is mitosis made up of
Prophase
Metaphase
Anaphase
Telophase
describe what happens in G1 and G2
- Gap (growth) phases – need to grow so they can make two cells out of one cell
- Longest phases
- No synthesis of DNA
- Cell has checkpoints and the cell will not progress unless they are met
- Replication of organelles happen in G1 and production of proteins, cytoplasm and nucleotides
- G2 – cell double checks DNA has been copied properly and checks for errors, if they are unable to repair errors then the cell undergoes apoptosis
- G1 - Cell checks the environment both internally and externally – make sure that the external environment is correct around the cell so it can receive the daughter cell
what happens in S phase
- Synthesis phase
- DNA is duplicated
- 2n to 4n – sister chromatids, each chromosome replicates
- chromosome are held at the centromere, so they are not mixed up at this point
- need 4N for two of the daughter cells
- semi-conservative replication
- this is where mutations can occur
what is the interphase phase the cell spends most of the time in
G1 and G2
what happens in prophase
- DNA condenses to form chromosomes that are joint at the centromere
- Nucleoli disappears
- Nuclear envelope breaks down – chromosomes need to go into the main part of the cell,
- Centromere is a specialisation of the histones, this is an attachment point onto the microtubules
- Centrioles are special hollow structure that organise the microtubule assembly, organise mitotic growth spindles
- Centrioles separate and move apart towards opposite poles and organise the production of microtubule filaments
- Mitotic spindles start to appear and grow towards the equator of the cell
- Microtubules form a radiating array
- Chromosomes are attached to the microtubules by kinetochore
describe the process of metaphase
- Chromosomes are lined up in the metaphase plate
- Centrosomes are at polar ends
- Microtubules and centromeres bind together to form kinetochores
- Kinetochore/microtubules are used to pull chromosomes apart, one from each pair of sister chromatids pulled towards opposite ends
- Cohesion are now only present in centromere to hold sister chromatids together
Describe the process of anaphase
- When chromosome reaches centrosome, the poles separate further by elongation of the polar microtubules
- Cohesin is hydrolysed and it is not functional anymore this allows separation
- they are pulled to polar ends
describe telophase work
- Uncoiling of chromosomes
- Reformation of nuclear envelope
- Contractile ring forms of actin and myosin pinches the cell until it splits into 2 daughter cells , cytoplasm is dividing and division is completed
where does crossing over take place
- Takes place in prophase 1 between homologous pairs of non-sister chromatids
- Crossing over of tails which is called chiasmata
How do we regulate cell cycle progression
- Cyclin dependent kinases (Cdks)
- Cdks are activated by cyclins
- Specific cyclin-Cdk complexes act at different parts of the cell cycle
- The combination of cyclins and CDKs produce energy required for the cell to progress to the next stage
how is an cDK activated
Cdk
- Breaks down ATP and releases a phosphsate
- phosphate given to substrate that binds to cyclic and activates Cdk
- CKIs inhibit CDKs
What proteins block the G1/S phase transition
- CKI proteins (p16, p21, and p27) primary act to block the entry into the cell cycle and the G1/S transition
what are the cell cycle checkpoints
1st - end of G1 - restriction point G1/S
2nd - end of G2(finished by end of G2) G2/M
3rd - metaphase - spindle checkpoint M
what are the 3 types of chemotherapy drugs (drugs used to control the cell cycle)
- Anti-mitotics
- biologics
- anti-hormonal drugs
describe how anti-mitotic work
- tradition chemotherapy drugs
- Anti-microtubule agents
- Affect all the dividing cells either tumour cells or human cells - non selective
There are two main classes - Vinca alkaloids prevent the formation of the microtubules therefore metaphase cannot occur
- Taxanes prevent the microtubule disassembly , chromsooems do not dissociate from the spindles and the cell cannot enter telophase
Describe check point 1
1ST check point (restriction checkpoint) Cell growth checkpoint (G1/S)
- Occurs at the end of G1
- Checks cell size, growth factors, DNA damage, nutrients
- Controlled by CKI, p16, which inhibits CDK4/6 so it cannot bind to cyclin D
- If not cell goes through resting phase until it was ready to divide
Describe check point 2
2nd check point - DNA synthesis checkpoint – completed by the end of G2 (G2/M)
- Occurs end of G2
- Checks cell size, DNA damage, and DNA replication
- Uses a phosphatase to remove a phosphate from cyclin B/CDK 1 complex as the phosphate is acting as an inhibitor
- If there is damage to DNA, or incorrect replication the cell cycle would be stopped
- Cell continues onto mitosis
Describe check point 3
Mitosis checkpoint – occurs during metaphase
- Spindle checkpoint
- Checks whether chromosomes are attached to spindles
- Tension in microtubules causes the initaiton of anaphase
