aging and disease Flashcards
why does cancer occur more often (60%) in 70> years?
due to accumulation of DNA damage
what are tumour suppressing genes and give an example?
p53= normal genes that encode proteins that prevents cell proliferation.
these genes are completely lost if proto- oncogenes complete gain of function recessive to oncogenes. e.g. p 53
what is proto-oncogens and oncogenes genes?
proto-oncogenes- normal genes involved in cell growth/ division
proto-oncogenes to oncogenes is a dominant gain of function mutation.
oncogenes- is a porto-oncogene activates by a mutation or over-expression
the three methods to convert from proto-oncogene to oncogene?
1) deletion/point mutation
2) gene amplification
3) chromosomal rearrangement
1) normal cells- active protein RAS causes cells to divide. it turns off.
cancer cells- hyperactive RAS cannot be switched back to inactive form (causes 30% of cancers)
2) normal protein is really overproduced (cell proliferation)
e.g. the transcription factor ‘Myc’
3) breaking or re-joining of different chromosomes
Knudsons two hit hypothesis - retinoblastoma (Rb)
loss of a single gene in Rb is a key step to developing a tumour in retina
sporadic Rb= 60% of cases
develops in children with no family history in one eye.
(two mutations in each allele must occur for loss of tumour suppressing gene p53)
hereditary Rb= 40% of cases
occurs earlier with tumours in both eyes.
two mutations in each allele must occurs. 1 is inherited. 1 is somatic.
why retroblastoma occurs (using the cell cycle)
DNA damage puts a halt on G1 checkpoint therefore normal cells won’t progress into S phase.
this is controlled by Rb
Rb blocks cell cycle progression by inhibiting E2F transcription factors when unphosphorylated.
the function of BRCA 1 protein?
required for normal DNA repair. the loss of function mutation results in an accumulation of mutations then cancer
how can a loss of function mutation in BRCA 1/2 lead to breast cancer development?
-sporadic
-familial
sporadic breast cancer- older women
one tumour in one breast
familial (BRCA 1 mutation : heterozygous)
younger women
multiple tumours in both breasts
how is replicative immortality enabled through the enzyme telomerase?
cancer cells increase action of telomerase therefore cancer cells don’t die off as telomerase is always adding back genomic DNA which is lost.
allowing telomerase to maintain the length while they proliferate.
enzyme is only supposed to be active during early stages of embryonic development
what is angiogenesis in normal cells and cancer cells?
normal cells- involved in growth development and wound healing
cancer cells- cancer cells require new blood vessel formation to survive and grow so infiltrate capillaries to grow tumour.
what is hypoxia - inducible transcription factor (HIF)
switches on in low oxygen environments
regulates 100s of genes that induces angiogenesis e.g. VEGF
why is angiogenesis an advantage to growing tumours ?
-instravasation
-extravasation
-metastasis
intravasation- cancer cells break down capillary wall entry into blood vessels (can be destroyed by a healthy immune system)
extravasation- exit of cancer cells from blood vessels to invade secondary organs
metastasis- spread of cancer cell to another part of body
describe tamoxifen - drug for breast cancer.
describing normal oestrogen then the presence of tamoxifen
normal- oestrogen molecules bind to receptor and changes receptor change. to allow co-activators to bind as act as transcription factor
tamoxifen- tamoxifen molecule binds to receptor but does not change the receptor shape. therefore tamoxifen receptor cannot bind to co-oactivators.
=cell proliferation does not happen.
what is the HER2 gene and how does the Herceptin drug for breast cancer target this?
HER2 causes gene amplification and receptor over expression in 25% of breast cancer.
Herceptin targets HER2 oncoprotein.
how does the drug anastrozole inhibitor prevent breast cancer?
blocks oestrogen production therefore will not cause cell proliferation within the breast
