Flashcards in Food and Cancer -L9 Deck (45):
How many different types of cancers are there?
cancer is a collection of related diseases of about >200
Why do most cancers start in epithelial cells ?
because this cell type divides more often
What are the important aspects of cancer?
requires multiple mutations - within DNA
uncontrolled cell division as cells dont respond to stop signals
may damage surrounding organs- this is when tumours start being a problem
metastasis- causes serious problems
process of initiation of tumours in an organism
tissue composed of cells that deviate from normal program of cell division and differentiation
define benign tumour:
tumour cells remain in a single mass and do not invade or disrupt surrounding tissues
define malignant tumour:
tumour cells invade and disrupt surrounding tissues
spread of malignant tumour cells throughout the body - normally through blood and lymphatic system
What does it mean by cancer cells are defined by their origin ?
they will act like the cell type from their origin wherever they appear
e.g. breast cancer cells act like breast cancer cells wherever they are
What pathway can lead to cancer ?
1) mutation inactivates TSG
2) cell proliferates
3) mutations inactivates DNA repair gene
4) mutation of proto-oncogene creates an oncogene
5) mutation inactivates several more TSG
What mutations most commonly occur in cancers?
most cancers result from mutations in cellular genes
other cancers are caused by viruses - viruses can insert their DNA into our DNA
- mutations occur in genes involved in cell division
What are cancers of epithelial cells, bones and muscle cells?
bone and muscle= sarcomas
How much of cancers are sporadic ?
- only a small proportion are genetically related
What does cell differentiation correlate with ?
loss of ability to proliferate - highly specialised cells are terminally differentiated
What is required for a cell to undergo differentiation ?
it has to divide and during this it alters itself, altering the proteins it is going to produce
but once a cell is terminally differentiated then it will no longer divide because it is highly specialised - they are replaced by new cells
What signalling molecules control normal cell cycle ?
growth factors- stimulate cell division
growth-inhibiting factors- inhibit cell division
What signals are cancer cells unable to respond to ?
unable to respond normally to intra-cellular and/or extracellular signals that control cell proliferation, differentiation and ultimately cell death
What are the frequency of genetic mutations that can occur in different types of cancer ?
can be as few as 2 to at least 6 mutations - likely that more occur during the disease to increase malignancy
Why do not all mutations lead to cancer?
sometimes mutations can be fixed, may not cause a change, some are beneficial (evolution), majority of DNA is not involved in cell division
What are the 6 stages of cancer progression ?
1) loss of growth signal automomy
2) evasion of growth inhibitory signals
3) evasion of apoptosis
4) unlimited replicative potential
5) angiogenesis- tumours develop blood supply which is a key part to tumours being successful
6) invasion and metastasis
According to the IARC how many factors are there that are carcinogenic to humans ?
- many are related to occupation
- many are unavoidable
Not all mutations will lead to cancer because...
-mutation is repaired
-mutation is not repaired but it is not in a "bad" place
-mutation is in a bad place is not recognised but is dealt with and recognised by defines systems
How many mutations occur in our DNA everyday ?
10,000 mutations per day in human
1 in 1000 in these changes survives because they are repaired by one of a number of different DNA repair enzymes - these are critical
What would a a really bad thing associated with DNA repair systems?
if they suffered mutations and their efficiency was reduced- defects or inefficiencies of the DNA repair system will increase the number of mutations increasing the likelihood of cancer
HOWEVER stimulating their efficiency would be a good thing
What is one of the most common inherited cancer syndromes?
hereditary non-polyposis colon cancer
results from defects in mis-match repair- with at least 5 different mismatch repair genes involved
- it develops at an early ages
What 3 types of genes are frequently mutated in cancer?
1) proto-oncogenes to oncogenes
2) Tumour suppressor genes
3) genes linked to mutation rate- any gene that increases mutations occurring
How many different oncogenes have been discovered and what is their purpose?
about 100 different oncogenes
all proto-oncogenes are involved in positive control of cell growth and division
What are the 2 classes of proto-oncogenes?
growth factors= regulatory genes involved in the control of cell multiplication
protein kinases= add phosphate groups to target proteins, important in signal transduction pathways
How were oncogenes originally discovered?
discovered in tumour-causing viruses but then found to be similar to or derived from genes present in animal host cells called proto-oncogenes
What are oncogenic mutations like ?
mutations that produce oncogenes are genetically dominant
oncogenic defect can be in any of the proteins in communicating the "divide" signal e.g. growth factors, transmembrane proteins, cytoplasmic proteins, nuclear transcription factors
What is Ras and what is the issue with it ?
it is a mutant form of a G protein which is common in tumour cells
- ras oncogene is always active and encodes a protein with normal GTP binding but not GTPase activity and therefore this is why it is always active - this means unregulated growth
What % of lung, colon and pancreatic cancer are associated with ras mutations ?
30-50% lung and colon
What do defects in TSGs cause?
removes the normal restraints on cell division
defects in one or more TSGs can lead to tumour formation
mutations in TSGs are genetically recessive - therefore if you inherit one correct copy and one defective copy you won't be diseased
How many cancers have mutations in p53 gene?
half of all known cancers
What is p53?
it is a transcription factor with greater than 100 different target genes
mutations lead to increase half life
How does unregulated growth occur ?
-gain of function mutations of proto-oncogenes producing an oncogene
-loss of function mutations in TSGs
LOF are more common but both alleles must be involved as it is genetically recessive
What are the stages of colorectal cancer ?
1) normal colorectal epithelium - altered by a TSG
2) early adenoma- oncogene produced
3) intermediate adenoma- maybe another TSG mutated
4) advanced adenoma- p53 mutation
5) colorectal carcinoma
6) invasive carcinoma
7) metastatic carcinoma
Numerous different mutations at each stage - the effects of mutations are not all or none
What are the GOF mutations identified in colon cancer and what function do they affect?
- alters signal transduction
What are the LOF mutations identified in colon cancer and what function do they affect?
- alter cell adhesion
- alter proliferation and differentiation
- alter DNA repair and apoptosis
- alter DNA repair
Why is apoptosis so important in cancer and tumour formation ?
because for a tumour to be successful it needs to have inactivated apoptotic processes
both the intrinsic and extrinsic pathways can have alterations in them - many have inactivated the p53 pathway
REACTIVATING this apoptic pathway is a key research area
What are telomeres?
repeated sequences of DNA that protect the ends of chromosomes
What is the end replication problem ?
it causes DNA damage and activates p53
How is senescence induced?
induced by telomere shortening
What does the inactivation of p53 cause?
it forces the cell to enter crisis instead of senescence