Please enable JavaScript.
Coggle requires JavaScript to display documents.
CANCER (cells escaped from cell cycle control (ref. mitosis)…
CANCER
cells escaped from cell cycle control (ref. mitosis)
divide excessively without control
normally, cells don't continuously divide (exist in G0 phase)
only divide when growth, replacement of damaged or dying cells is needed
determined by cell signals
CHARACTERISTICS (ref. pg 11 of notes)
normal cells need growth factors (hormones/proteins signalling cell growth)
cancer cells don't need growth factors
divide without growth factors - divide continuously because of a lack of regulation
independent cells
inhibition of synthesis of growth factors by cell regulation stops cell division
normal cells stop cell division when in contact with other cells
loss of contact inhibition in cancer cells
grow even after the touch other cells
large mass of cells formed
normal cells age and die via apoptosis
replaced by new cells
cancer cells undergo unlimited number of cell division without triggering apoptosis
telomerase is active (never reach critical telomere length to trigger apoptosis)
unregulated cell division
normal cells undergo apoptosis when DNA is irreversibly damaged or abnormal cell division
cancer cells continue to divide despite DNA damage or abnormal cell division
accumulation of damaged DNA
MULTI-STEP DEVELOPMENT OF CANCER
all regulation checkpoints must be inactivated
G1 checkpoint
G2 checkpoint
M checkpoint
one mutation in a tumor suppression gene or protooncogene is not enough
Each mutation drives a wave of cellular multiplication associated with gradual increases in tumor size, disorganization and malignancy
accumulation of multiple (4-6) independent mutations
in cell cycle regulatory genes
of at least one proto-oncogene
of multiple tumor suppressor genes
single cell suffers a mutation in a gene involved in the cell cycle (first mutation)
mutated cell predisposed to proliferate excessively (slight growth advantage)
eg. tumor suppression gene causes loss in function
cell does not undergo apoptosis
mutation is passed on to all daughter cells by mitosis
second mutation by descendant cells
deregulation of cell cycle
cell proliferates too much
1 more item...
third mutation (in subsequent generations)
cell proliferates more rapidly and has structural changes
fourth mutation (subsequent generation)
2 more items...
accumulation of. mutation
forming a malignant tumor
starts with benign tumor
cell grows uncontrollabley
localised tumor
easy to kill
breakthrough and invasion
malignant cells invade neighbouring tissues, blood vessels
because they have proteases that digest extracellular matrix (allows entry)
increased cell-matrix adhesion, decreased cell-cell adhesion
metastasis
spread throughout the body by circulatory or lymphatic systems
invade normal tissue
migrate to other parts of the body
nutrients and oxygen is needed
malignant turmors need to undergo
angiogenesis
mutations induce angiogenesis
formation of new blood vessels
supply nutrients and oxygen to growing tumor at new site
CAUSES
internal factors
loss of immunity
functional cytotoxic T cells remove cancer
cells infected by viruses (insertional mutagenesis)
transformed cells that haven't adapted to evade immune detection system
loss in immunity increases change of cancer cels multiplying (lowers regulation)
genetic predisposition
born with germline mutation (defective tumor suppressor gene)
hormones
required for tumors to grow
external factors
chemical carcinogens
damage or alter DNA
UV and ionising radiation
causes nitrogenous bases to be more reactive (point mutations?)
penetrates nucleus and forms damaging ions in cell
breaks or mutates DNA (chromosomal rearrangement)
viruses
human papillomaviruses (HPV)
human immunodeficiency virus (HIV)
agents stimulating mitosis rate (eg tissue injury)
agents causing chronic inflammation
generates DNA damaging oxidising agents in cell
PROCESS OF FORMING
mutations in genes regulating cell division cycle
results in uncontrolled cell growth and division
PROTO-ONCOGENES
code for proteins that send signals stimulating cell growth and division
growth factors, receptor proteins (for growth factors), intracellular protein kinases, transcription factors
G PROTEIN
ras protein (coded by ras gene)
regulated by GTP and GDP
binding of growth factor triggers GTP displacing GDP
Active ras protein passes on signal to cytoplasmic kinases
2 more items...
turned off when ras protein hydrolyses GTP to GDP
when GDP is bound, ras is inactive
when GTP is bound, ras is active
negative or positive control?
mutated to form hyperactive ras protein
point mutation in coding region
change in 3D conformation of ras protein
1 more item...
when turned on at the wrong time
function as oncogenes (cancer genes)
code for proteins leading to overstimulation of cell growth and division
gain of function mutation
occurs in dominant mutations (single copy of oncogene expresses the trait)
dominant allele
caused by
point mutations
in coding regions
2 more items...
in regulatory region (promoter)
1 more item...
chromosomal rearrangement
translocation (breakage and rejoining) of DNA
2 more items...
gene amplification (gene level)
errors in
DNA replication
produces many extra gene copies
2 more items...
insertional mutagenesis
insertion of a retrovirus into the DNA
2 more items...
TUMOR SUPPRESSOR GENES
code for proteins sending signals to
prevent cell division
halt cell cycle
carry out DNA repair
cause apoptosis (cell death)
important in interphase (ref. G1)
have a loss of function mutation
genes no longer inhibit cell growth
recessive mutation (on recessive allele of gene)
only when there is a loss in heterozygosity (normal allele is lost) will tutor suppressor gene be expressed
case study: P53 tumor suppressor gene
codes for P53 transcription factor (protein)
function: regulation
hold cell cycle in G1 checkpoint
recognises DNA damage
1 more item...
initiate apoptosis (programmed cell death)
mutation causes non-function p53 proteins to be synthesised
p53 cannot carry out functions
