genetics discussion 4 (cancer) Flashcards
Why do tumour suppressor genes usually require both alleles to be mutated before there is an increased cancer risk?
Tumour suppressor genes ARE RECESSIVE
tf INACTIVATION OF BOTH alleles are REQUIRED
If one gene is unaffected,
it will be functional
thus suppress tumours.
What are 2 reasons why mutations in Ras are important in tumour formation?
- The protein that is coded by Ras gene,
is present in many SIGNAL TRANSDUCTION PATHWAYS
- eg. MAPK pathway
which are IMPORTANT IF CELL REGULATION (differentiation, proliferation and apoptosis). - Ras is a GENE that has the
MOST FREQUENT PROTO-ONCOGEN MUTATION
What are 2 reasons why epithelial cells are a common tumour cell type?
- Epithelial cells such as skin are
MOST EXPOSED to the external environemnt causing mutations
- by UV rays - In areas such as PROSTATE there is
HIGH TURN OVER of EPITHELIAL CELLS, t
his means there is MORE PROLIFERATION hence
HIGH CHANCE OF MUTATION
Why is one mutated allele of an oncogene sufficient to increase cancer risk?
==> Because AFTER THE MUTATION of a normal gene into oncogene, ==> there is either - CHANGE the DNA SEQUENCE - or it will INCREASE GENE EXPRESSION
==>As the mutation occurs, the oncogene will have an >>> INCREASE PROTEIN FUNCTION which will - INCREASE ACTIVITY of the protein, - INCREASE the STABILITY of protein - INCREASE PROTEIN EXPRESSION (which has a loss of control of transcription.)
> > > increase the risk of cancer.
Why are mutations in the MAPK pathway commonly found in tumour cells?
The MITOGEN-ACTIVATED PROTEIN KINASE (MAPK) pathway is involved in
- process of mitosis.
==> mutation in this pathway
==> CELL DIVISION may become UNREGULATED
»> leading to the development of a tumour.
p53 is a protein that prevents cell division when DNA is damaged. How is it regulated in the cell?
p53 mutation = NO BRAKE pedal
==> non functional p53 gene
==> produces a non functional p53 protein
==> tf don’t get the DNA check we should get (w normal p53)
==> tf fails to stop cell division of damaged cells & no DNA repair
==> so if there is an error, there is nothing to stop the cells from dividing
==> enough errors built up
»> cancer
The main regulator of p53
= MDM2.
In normal cells ==> p53 is regulated by ==> binding of MDM2 proteins. ==> This inhibits the activity of p53 ==> and encourages p53 degradation.
In a damaged cell
=> levels of p53 increase
==> followed by an increase of MDM2
==> However, MDM2 is not effective on p53 if
phosphorylated with protein kinases (eg. ATM).
Once the damage has been fixed in the cell.
==> Proteins inactive = dephosphorylation of p53
==> allows the built up MDM2 to bind
==> stop p53 protein
Why is p53 only activated in cells with damaged DNA?
==> DNA is damaged it ==> trigger the increase of p53 protein ==> as its functions of growth arrest ==> stops the cell cycle ==> prevents the damaged DNA from further replication.
During the growth arrest period
==> p53 may activate proteins to help repair the DNA.
==> The last resort is apoptosis
»> avoid the reproduction of cells w damaged DNA
Why do you think several mutations are required for a cell to become a tumour?
It requires ==> many of the various genes ==> that control cell proliferation to ==> become mutated and >>> cause a tumour due to the lacked signalling for apoptosis.
Thus mutations in
- tumour suppression genes are also required
along with the
- mutations causing unregulated growth.
Which type of cancers are more common and why?
CARCINOMAS
because they involve EPITHELIAL CELLS
- are more rapidly growing and
- display higher rates of mutation.
How is a proto-oncogene different to an oncogene?
proto-oncogene = considered a normal gene involved in functions within the cell such as signals - leading to cell division and - regulation of apoptosis,
==> but when altered by mutation,
==> becomes a oncogene
==> that can contribute to cancer.
3 ways oncogene code for protein leading to uncontrolled cell division
oncogene c. uncontrolled cell div
- alter RECEPTOR for growth =>STAYS ACTIVE (membrane receptor),
- UPREG cytoplamic SIGNALLING of growth (cytoplasm)
- UPREG activity => TRANSCRIPTION FACTORS (nucleus)
How could an enzyme that is normally in the cytoplasm be oncogenic?
= Mutated forms TYROSINE KINASE
could STAY ACTIVATED,
thus signalling CONTINUOUS GROWTH
Why can chronic myeloid leukemia
be treated by a DRUG THAT INHIBITS the cytoplasmic TYROSINE KINASE produced in this cancer?
How and why is this safer than forms of cancer therapy involving chemotherapy or radiation?
“GLIVEC” (anticancer med)
==> blocks specifically mutated tyrosine kinase
==> but not unmutated enzyme.
This is safer as it is SPECIFIC and
does NOT INDUCE OTHER MUTATIONS
(like chemo & radiation)
Name three ways a tumour suppressor protein could inhibit tumour growth.
1, Activate DNA DAMAGE REPAIR
2, PREVENT CELL DIVISION
when DNA damage is recognised
- INITIATE APOPTOSIS
if DNA damage cannot be repaired
A liver cancer is found.
How can we determine whether it is the primary or secondary cancer?
BLOOD TEST can measure the BIOCHEMICAL PROFILE of the tumour.
A SECONDARY tumour will have a
biochemical profile SIMILAR TO ITS ORIGIN (of cancer)
eg. For instance alpha-fetoprotein (AFP) is produced by liver cells,
secondary brain tumour=
if a BRAIN TUMOUR is ACCOMPANIED BY AFP
that may indicate
it is secondary to a (primary liver tumour.)
