Complete set of notes for this element in the Bristol A100 Pre-clinical course. This is everything you need to know to achieve 90% marks. It is presented in a simple question, simple answer layout. If you have any questions or if anything doesn’t make sense, email me at mh14782@my.bristol.ac.uk....
Table of Contents
ELEMENT 9 – THE MOLECULAR BASIS OF CANCER .............................................................. 1
9.1: Introduction to Normal Cell Growth .................................................................................... 1
9.2: Cell Growth, Differentiation and Apoptosis......................................................................... 3
9.3: Oncogenes & Tumour Suppressor Genes ............................................................................. 6
9.5: Classification of Tumours ..................................................................................................... 8
9.6: Multistage Development of Cancer.................................................................................... 10
9.7: Cancer Immunology ........................................................................................................... 11
9.8: Cancer Spread ................................................................................................................... 14
9.9: Cancer Causing Agents ....................................................................................................... 15
9.10: Hormones & Cancer ......................................................................................................... 18
9.11: Cancer Prevention ........................................................................................................... 19
9.12: Treatment of Cancer ........................................................................................................ 20
ELEMENT 9 – THE MOLECULAR BASIS OF CANCER
9.1: Introduction to Normal Cell Growth
• What is a neoplasm? The result of neoplasia. A neoplasm is an abnormal mass of tissue, the growth
of which is uncoordinated with that of normal tissues due to genetic alterations. Growth continues
even if the ‘growth stimulus’ is removed.
• What is a tumour? A swelling. To clarify, not all swellings/tumours are neoplasms, and not all
neoplasms form swellings/tumours.
• What is cancer? Cancer is a disease where cells grow out of control and invade, erode and destroy
normal tissue. It is a malignant neoplasm
• What are the differences between benign and malignant neoplasms?
Characteristic Benign Malignant
Size Small Large
Borders Clear borders, often Poorly defined
encapsulated
Differentiation Resembles original tissue Variable
Growth rate Slow Fast
Mitotic figure Few, due to slow growth rate Many, due to high growth rate
Necrosis No Yes
Invasion No Basement membrane invaded.
Neoplasm invades local structures
Metastasis No They can do, yes.
• What is the cytoskeletal structure of a typical cell
nucleus? Nuclear lamina inside the nucleus and
disorganised intermediate filaments surrounding it.
• Revise what telomerase does.
• Revise the structure of the nucleosome (6.1)
,• What does the histone H1 protein do? It acts as a clamp on the nucleosome, pulling the adjacent
nucleosomes together too. See the difference between the 2nd and 3rd bits on the diagram to see
what I mean by ‘pulling together’.
• What are the phases of the eukaryotic cell cycle?
1. G1 – growth and replication of organelles. The cell
can divert to G0 phase at this stage, where it
pauses in the cell cycle
2. S – synthesis of new DNA before replication
3. G2 – checks replication is complete and correct
4. M – mitosis and cell division. The only stage not
also referred to as interphase.
• What are cyclin dependent kinases, CDK? They’re a family of
kinase enzymes that regulate the cell cycle. In order to be able to
phosphorylate things, they must be bound to their specific
partner cyclin. Each CDK has its own cyclin that it needs to be
bound to. The levels of CDK-cyclin complexes vary
constantly depending on the cell cycle stage that the cell is in
(hence the name cyclin). CDK-cyclin complexes can phosphorylate substrates to control the cell
cycle, or Cyclin-CDK complexes in an earlier cell-cycle phase can help activate cyclin-CDK complexes
in a later phase.
• What CDK complexes with what cyclins activate which stages of the cell cycle?
Stage CDK (Goes down in order) Cyclin needed (Remember DEAB) Name of CDK-cyclin complex
G1 CDK 6 & CDK 4 Cyclin D G1 CDK
G1 à S CDK 2 Cyclin E G1/S CDK
S CDK 2 Cyclin A S CDK
M CDK 1 Cyclin B M CDK
• What CDK is responsible for pushing the cell past the R
point? CDK 6 & 4 with the needed cyclin D = the G1 CDK
• What is the R point? The restriction point is the point in the cell
division cycle the cell stops so that it can double check itself,
unless told to move on by G1 CDK
• Are the levels of cyclins always the same in the cell? No,
they’re being constantly synthesised or broken down
depending on the cell cycle stage (i.e. when they’re needed)
• What do the following CDK inhibitors (CDI) inhibit?
• CDI • CDK complex it inhibits
• p27 • G1/S CDK and S CDK. It inhibits these before they are fully in their
prime, in the G1 phase so cell withdraws from cell cycle
• p21 • G1/S CDK and S CDK. It inhibits these after DNA damage in G1
phase
• p16 • G1/S CDK. Inhibits this in G1 phase
,• What type of protein are CDIs? Tumour suppressor proteins, as they prevent replication
• In human cancers, what CDK is commonly suppressed? As can be seen from the table above, G1/S
CDK (made up of CDK 2 and cyclin E) is commonly suppressed.
• What happens if the cell is found to not be perfect at the R point, or at the G2 checkpoint just
before mitosis? The cell dies
• What does the retinoblastoma protein do? It binds to transcription factor E2F, which is a
transcription factor and would hence promote progression through the cell cycle. When E2F is
bound to Rb, it is inactive. When it is free from Rb, it stimulates progression through the cell cycle as
it’s a transcription factor.
• How do cyclin CDK complexes actually regulate the cell cycle/make it continue? All we’ve said so
far is that it’s a kinase but what does this actually do? All we need to know is how the G1 CDK
(cyclin D with CDK4/6) pushes the cell through the R point:
1. Retinoblastoma protein is bound to E2F, preventing E2F from stimulating cell progression
(see above)
2. The cyclin-CDK complex phosphorylates Rb
3. This indices a conformational change in the Rb
4. Rb can no longer bind to E2F
5. E2F is released
6. E2F stimulates progression through the cell cycle, past the R point
9.2: Cell Growth, Differentiation and Apoptosis
• What’s the difference between labile cells, stable cells and permanent cells? Lecture 8.8 covered
this:
• Cell Type • Explanation • Example
• Labile • Constantly proliferating –• Stratified surfaces such as the skin and the GI
constant in cell cycle tract
• Stable • Don’t normally • Viral hepatitis – when there is acute inflammation
divide/divide very slowly, of the hepatocytes, there is regeneration and
but can divide more repair as the cells divide. NB: If infection is
, quickly when they need chronic, with multiple infections, cirrhosis can
to – cells in reversible G0 occur
• Permanent • Never proliferate – cells • Neurons and cardiac muscle cells
in irreversible G0
• Rank the above types of cells in susceptibility to cancer. Labile > Stable > Permanent because of the
frequency of division
• Describe the asymmetrical proliferation of cells surrounding the villi in the small intestine.
1. Stem cells in the crypt divide constantly
2. Half of the daughter cells stay stem cells that continue to
divide and maintain the number of stem cells in the crypt
3. The other half start to
rise up the villus and
differentiate, but will
no longer divide
4. Epithelial cells that
cover the villi therefore
do not replicate, as
they are terminally
differentiated
• What are transit-amplifying
cells? From the base of the
crypts up: Stem cells à transit
amplifying cells à differentiated epithelial cells. Transit amplifying cells are not differentiate yet but
are committed to becoming differentiated.
• What type of stem cell type is found in the crypts of the small intestine? Unipotent stem cells, as
they can only produce that one tissue type. There is usually a small proliferating stem cell population
in a given tissue
• How do cells know what to differentiate into, seeing as all cells have the same genotype? The
differential activation and suppression of genes, which is dependent on the tissue
type, developmental stage of the organism and general environment.
• What is a Paneth cell? A cell in the intestinal epithelium involved in the innate
immune system because it has antimicrobial contents
• Define the following terms
Term Definition
Hypertrophy Size of cellsñ, number of cells constant à tissue gets bigger
Hyperplasia Size of cells constant, number of cellsñ à tissue gets bigger
Hypoplasia Partial failure of tissue to develop
Aplasia Complete failure of tissue to develop
Atrophy Regression in tissue size, having been fully developed
Degeneration Wasting away with decay
Metaplasia Replacement of one cell type with another
Dysplasia Abnormal proliferation (not cancer, but can develop into it)
Anaplasia Cells change morphology so that they don’t look like each other or like
the original cell type. It’s the highest level of being undifferentiated
(note: not aplasia!)
• What type of cell death does radiotherapy and chemotherapy aim to achieve in neoplastic cells?
Apoptosis because it causes no inflammation (remember when a cell undergoes apoptosis, the cell is
broken down into small apoptotic bodies, which is eaten by macrophages)
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