The biology of cancer part 2 Flashcards
name endogenous chemicals
- reactive oxygen species
- reactive nitorgen speciies
name exogenous chemicals
tobacco
chemicals
name substances that can cause cancer
Endogenous (reactive oxygen and nitrogen species) and exogenous chemicals(tobacco chemicals)
Radiation (UV)
Biological attack viruses and bacteria (repairs of DNA should be carried out swifty before cells have chance to divide)
why does carcinorgeneis occur
Multistep process
Mutants accumulate stepwise over time additional mutations may confer a growth advantage
A tumour may contain heterogenous mix of cells which are sub clones derived from original
Cancer instance increases with age and more as cell division is undergone
Assists in metastasizing
Building accumulating effect
Health cells can pick up cancer - yellow dot
Gives growth advantages and accumulated a second initiating mutation shown in red
One of these cells have picked up a further initiating mutation should in green - 2 copies now
Primary cells have significant growth advantages and grow out and develop cancer
All cells in cancer arise from originating cells
Mutations will occur randomly
Outgrowth of certain subclones
Subcones are competing and out growing depending on conditions they require
Most treatment resistant or fastest dividing cells are those that will go on and predominate for that cancer
what are the 2 major types of mutated genes that contribute ti cancer
ONCOGENES- product of mutated gene has increased activity or produced in greater amount. Therefore acts in a dominant fashion.One mutant allele sufficient for effect.Unmutated forms are proto-oncogenes.
Tumour suppressor genes- mutated form will have a role in inhibiting growth and tumour formation . mutation leads to loss of function. Usually recessive
For increase growth a positive factor needs to be enhanced and negative suprress
Somatic cells have 2 copies of each gene- allele
describe kudosns two tie hypothesis
UMOUR SUPPRESSOR GENES- KNUDSONS TWO HIT HYPOTHESIS
Recessive nature predicted by knudson in 1971
Individual with inherited form - inhites 1 germline mutation
After birth - need somatic mutation for cancer initiation to begin
People tend to be much younger and only need one further mutation to get phenotype
Sporadic form- individual born with 2 health version
Both alleles mutated for recessive inhibitory effect to be released
Inherited form of retinoblastoma- increase risk of eye cancer
APC - gut cancer- regulate cell adhesion, help regulate corrective division of chromosomes
how many cancer associated with gremlin mutation
70
how many cancers associated with somatic mutation
342
what do oncogenes code
Growth factors
Components of signal transduction cascades,
Nuclear DNA-binding/transcription factors - bind to genes to switch on and off
Genes involved in DNA repair/cell-cycle control
Proto- oncogenes are normal cellular genes that can cause cancer when they become mutated to create an oncogene
describe the role of oncogene
Oncogenes might be activated by GF or receptor binding
Receptor may be mutated or bypass signal
Following binding, the signal has to be transmitted down through the cell to get to nucleus where protein kinase
Protein kinase are enzymes that carry out phosphorylation so they add phosphorus element to molecules
Phosphorylation is way of activating molecules
Kinases can be oncogenes and become more active to trigger phosphorylation
Once signal has passed through the cell the later stage of singly effects Transcription factors
TFs can also be oncogenes and eb mutated to become more active and bind to DNA more or biden at different site driving expression of genes
Driving the expression of genes push forwards cell cycle
Oncogenes can be involved in DNA repair
Apoptosis can be regulated by oncogenes
Help cell resist apoptosis
Increase in anti apoptotic genes- not die and have a long life span
TSG cna be linked to apoptosis - promote cell death
Mutated TSG result in to being able to initiate apoptosis
DESCRIBE RTK
Common e oncogene - e RTK
Receptor detected and bound to its intended growth factor - ligand
In its inactive unbound form , recept present in 2 monomers but when it binds to ligand it causes conformational change and monomers diamerise
Activating receptor
In the intracellular part of receptor= kinase domains
Dimerisation can activate kinase domains and can phosphorylate either parts for receptor - activation becomes GF bound
Adds phosphates to AA tyrosine
Become docking sites for other signalling pathways and molecules can dock and become activated passing on chain of phosphorylation that goes down all the way to effective TF and changed gene expression
Receptor helps to transmit signal across the cell - effects on gene expression
describe CDK4
CDK4 - CYCLIN DEPENDENT KINASE 4
Protein that controls cell division
When mutated - makes altered CDK4 protein that is abnormally overactive
Abnormal protein makes cells divide abnormally fast which can lead to tumour formation
Primarily associated with melanoma but alco breast cancer and myeloma
Cyclin D can also be overexpressed in breast cancer and SCC
Different cyclins different stages but can’t go backwards
Regulated entry and G1 phase
What has mutations of FBFR been associated with
many cancer
what has ERBB2 mutations linked to
lung
gastric
breast cancer
describe the p53
P53 gene encodes a trasnicitpon factor but is a tumour suppressor gene
Loss of heterozygosity of short arm of chromosome 17 has been associated with tumours of lung,colon and breast
The region of chromosome 17 includes the p53 gene
Mutations at the p53 locus occurs in cancers of colon,breast,liver and lung
P53 involvement in neoplasia more frequent than another other known tumour suppressor or dominant proto oncogene
Detect when cells are hyperproliferative
DNA DAMAGE
TELOMERE SHORTEN
HYPOXIDA
Active p53 brings number of effect that protects integrity
Induces expression of antioxidants
All functions can be disrupted
-cell cycle arrest
Senescence
Apoptosis
