Molecular Biology of Cancer Flashcards
(35 cards)
1
Q
Definition: Cancer
A
- disorder of cell growth that results in the invasion and destruction of healthy tissues by abnormal cells
2
Q
Definition: Checkpoint
A
- critical control point where stop and go-ahead signals can regulate the cell cycle
- cell monitors internal equilibrium
3
Q
Checkpoints in the Cell Cycle
A
- G1-S
- G2-M
- M
4
Q
G1 Checkpoint; what is assessed?
A
Assessment of CELL GROWTH
- Presence of growth factors; proteins required to stimulate cell division
- Adequate cell size; initiate DNA replication in S phase
- Nutrients availability
- Conditions are favourable for DNA replication
5
Q
G2 Checkpoint; what is assessed?
A
Assessment of DNA REPLICATION
- Results of DNA replication (by DNA repair enzymes)
6
Q
M Checkpoint; what is assessed?
A
Assessment of MITOSIS
- Formation of spindle fibre apparatus
- Proper attachment of spindle fibres to all kinetochores assiciated with centromeres of chromosomes
- enzyme, separase, cleaves cohesin molecules, allowing sister chromatids to separate; ensures daughter cells do not have extra or missing chromosomes
7
Q
What happens if DNA/chromosome damage is too severe to repair?
A
Cell initiates apoptosis (programmed cell death)
8
Q
Action of Growth Factors (Stimulatory pathway)
A
- Bind to cell surface receptor on plasma membrane
- Signal transduced into cell and relayed to nucleus
- Transcription and translation; production of protein that promotes cell division
9
Q
Action of Growth-inhibiting Factors (Inhibitory pathway
A
- Bind to cell surface receptor on plasma membrane
- Signal transduced into cell and relayed to nucleus
- Transcription and translation; production of protein that inihibits cell division
10
Q
Cell Cycle Regulators
A
- Proto-oncogenes
- Tumour Suppressor Genes
- Contact-dependent / density-dependent inhibition
- Platelet-derived growth factor
- Environmental factors (e.g change in pH, nutrients, temperature)
11
Q
Function of Proto-oncogenes
A
- promote cell division
12
Q
Examples of Proto-oncogenes
A
- Ras gene
13
Q
Function of Tumour Suppressor Genes
A
- inhibit cell division to prevent inappropriate cell growth
- initiate apoptosis
14
Q
Examples of Tumour Suppressor Genes
A
- p53 gene
- retinoblastoma (RB) gene
15
Q
Contact-dependent / Density-dependent Inhibition
A
- most cells require adhesion to a substratum to divide
Stop dividing when:
- Lose anchorage
- Close proximity to one another
NOT APPLICABLE TO CANCER CELLS
16
Q
Platelet-derived Growth Factor (PDGF)
A
- released when platelets come into contact with damaged blood vessels
- fibroblasts, the main cells of commective tissues, have receptors for PDGF
- binding of PDGF triggers fibroblasts in the area of the wound to divide repeatedly, causing it to heal
17
Q
Definition: Carcinogen
A
- any agent that can lead to cancer formation due to ability to cause DNA damage or disrupt cellular metabolic processes
18
Q
CAUSES OF CANCER
• 1A) Lifestyle and diet - SMOKING
A
- tobacco smoke contains carcinogens; polycyclic aromatic hydrocarbons (PAHs)
- PAHs can bind to DNA and form adducts
- formation of adducts can cause mistakes in DNA synthesis, introducing mutations to DNA
19
Q
CAUSES OF CANCER
• 1B) Lifestyle and diet - UNHEALTHY DIET
A
- diet rich in salted, pickled and smoked foods (e.g smoked fish, meats treated with nitrates)
20
Q
CAUSES OF CANCER
• 1C) Lifestyle and diet - FREE RADICALS
A
- are dangerous, highly reactive chemical compounds that can damage DNA and lead to cancer
- build-up in person’s body happens when one’s own biochemical mechanisms to reduce them are unable to keep up with their production; abundance of free radicals in system
21
Q
CAUSES OF CANCER
• 2A) Radiation exposure - IONISING RADIATION
A
- overexposure can cause DNA mutations, leading to cancer
- potential sources include medical diagnostic and therapeutic procedures
22
Q
CAUSES OF CANCER
• 2B) Radiation exposure - ULTRAVIOLET RADIATION
A
- radiation from the sun that reaches earth
- damages DNA by forming pyrimidine dimers through formation of covalent bonds between adjacent pyrimidine bases
- if damage remains unprepared, this distortion of the double helix results in improper base pairing during DNA replication; distinctive mutation patterns
23
Q
CAUSES OF CANCER
• 3) VIRAL INFECTIONS
A
- some cancers involve certain RNA and DNA viruses
- termed transforming viruses; can integrate their genomes into host DNA and transform normal cells into tumourigenic cells by activating proto-oncogenes or inactivating TSGs
- DONE BY:
1. directing expression of viral proteins that can inactivate TS proteins like p53
2. Introducing oncogenes
24
Q
CAUSES OF CANCER
• 4) GENETIC PREDISPOSITION
A
E.g breast cancer
- PREDISPOSITION is inherited, NOT the CANCER itself
25
Mutations that can bring about uncontrolled cell division
1. Over-expression of proto-oncogenes
2. Under-expression of tumour suppressor genes
3. Mutations in genes responsible for apoptosis
4. Exposure to mutagens
26
Definition: Proto-oncogene
- stimulatory gene; can be made overactive or active at inappropriate times
- mutations usually dominant as mutation in a single copy of the gene is sufficient to produce a stimulatory effect
27
Proto-oncogenes encode for gene products that promote cell growth such as:
- growth factors
- growth factor receptors
- transcription factors
- protein kinases
- inhibitors of apoptosis
28
Definition: Tumour Suppressor Gene
- inhibitory gene that can mutate to become less active
- mutation usually recessive as both copies of the gene must be mutated to produce inhibitory effect
- inhibit inappropriate cell growth and proliferation
29
Action of gene products encoded by TSGs:
- halt cell division when DNA is damaged
- trigger DNA repair to prevent accumulation of DNA damage
- maintain cell anchorage to substratum
- involved in cell signalling pathways that inhibit cell cycle
30
Loss of function mutation in p53
- p53 encodes for a transcription factor (p53 protein) that inhibits the cell cycle when cell incurs DNA damage or abnormalities in chromosome attachment are detected
- prevents proliferation of cells that have incurred DNA damage
- loss of function mutations in p53; cell growth and division continues and DNA damage is retained, increasing risk of cancer
31
Gain of function mutation in Ras gene
- Ras gene encodes for the Ras protein that relays signal for a growth factor from a receptor to a protein kinase cascade, giving rise to a protein that stimulates cell division
- pathway will not normally operate unless triggered by appropriate growth factor
- gain of function mutation in Ras gene; hyperactive Ras protein that triggers the protein kinase cascade even in absence of appropriate growth factor; results in increased cell division, increasing risk of cancer
32
Point-mutations / base-pair substitutions in PROTO-ONCOGENES
1. In CONTROL SEQUENCES (PROMOTER, REGULATORY SEQUENCES & ENHANCERS)
- increase in expression of gene
- increase in amount of gene product
2. In CODING REGIONS
- alter protein structure
- changes activity of gene product; more active and more resistant to degradation
33
Gene amplification in PROTO-ONCOGENES
- extra copies result from random over-replication of small segments of DNA
- increase in amount of gene product; uncontrolled cell division
34
Chromosomal translocation in PROTO-ONCOGENES
A) chromosomes that break and rejoin incorrectly are translocated from one chromosome to another
- proto-oncogene may end up next to an especially active promoter or control sequence
- increased transcription; increase in gene product
B) reciprocal translocation
- results in chromosome being shorter than normal
35
Multi-step process
- cells in malignant tumours no longer respond to cellular control mechanisms
- invasion; spread into neighbouring tissues from the primary tumour
- may travel to distant tissues and organs and establish secondary tumours via metastasis
- may also be carried to other body parts through blood/lymphatic system
- angiogenesis occurs (formation of blood vessels) to supply adequate O2 and nutrients, removal of waste products
